Stimuli In Healthy Individuals Research Articles

Interaction of perceived social support and childhood maltreatment on limbic responsivity towards negative emotional stimuli in healthy individuals

Childhood maltreatment (CM) is associated with increased limbic activity, while social support is linked to decreased limbic activity towards negative stimuli. Our study aimed to explore the interaction of perceived social support with CM, and their combined impact on limbic activity in negative emotion processing. A total of 130 healthy individuals (HC) underwent a negative emotional face processing paradigm. They were divided into two groups based on the Childhood Trauma Questionnaire: n = 65 HC without CM matched with n = 65 HC with CM. In a region-of-interest approach of the bilateral amygdala-hippocampus-complex (AHC), regression analyses investigating the association of CM and perceived social support with limbic activity and a social support x CM ANCOVA were conducted. CM was associated with increased AHC activity, while perceived social support tended to be associated with decreased AHC activity during negative emotion processing. The ANCOVA showed a significant interaction in bilateral AHC activity (pFWE ≤ 0.024) driven by a negative association between perceived social support and bilateral AHC activity in HC without CM. No significant association was observed in HC with CM. Exploratory analyses using continuous CM scores support this finding. Our results suggest that CM moderates the link between perceived social support and limbic activity, with a protective effect of perceived social support only in HC without CM. The lack of this effect in HC with CM suggests that CM may alter the buffering effect of perceived social support on limbic functioning, highlighting the potential need for preventive interventions targeting social perception of HC with CM.

Subliminal attentional bias modification training for itch.

Itch is unpleasant and induces the urge to scratch. This is adaptive to remove the itch-inducing stimulus from the skin. Accordingly, itch draws attention to protect our bodily integrity. Recent studies investigated whether attention is preferentially drawn towards its location, i.e., attentional bias (AB), and also whether this bias could be changed in healthy individuals. So far, results are mixed concerning the existance of an attentional bias towards itch stimuli in healthy individuals as well as the impact of modifications. However, available studies have typically focused on conscious processing and might miss preconscious aspects of attention and potential biases at these stages. This study included 117 healthy individuals who underwent a subliminal Attentional Bias Modification (ABM)- training for itch based on a dot-probe paradigm with itch- related pictures. Participants were randomly assigned to a training towards itch group, a training away from itch group and a control group. This was done by manipulating the itch-target congruency of the dot-probe task during a training block. Pre- and post-training assessments were regular dot-probe tasks. Exploratorily, also attentional inhibition, cognitive flexibility and itch-related cognitions were assessed. Lastly, participants received an itchy stimulus on the inner forearm before and after the ABM-training to assess potential effects on itch sensitivity. Results showed no AB towards itch across groups at baseline, i.e., pre-training, but an AB away from itch, hence, avoidance of itch, post-training. Further analyses showed that this effect was driven by an attentional bias away from itch in the control group, while there were no significant effects in the experimental groups. There was no effect on itch sensitivity. These findings are in line with recent studies on conscious ABM-training for itch and pain that also did not find significant training effects. Therefore, it is suggested that the field of AB might need to reconsider the current assessment of AB. Moreover, AB is probably a dynamic process that is highly dependent on current itch-related goals and relevance of itch in a specific situation. This suggests that processes probably differ in patients with chronic itch and that also ABM-training might work differently in these populations. https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7561, identifier NTR7561.

Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants’ threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants’ treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.

Overly Strong Priors for Socially Meaningful Visual Signals Are Linked to Psychosis Proneness in Healthy Individuals.

According to the predictive coding theory of psychosis, hallucinations and delusions are explained by an overweighing of high-level prior expectations relative to sensory information that leads to false perceptions of meaningful signals. However, it is currently unclear whether the hypothesized overweighing of priors (1) represents a pervasive alteration that extends to the visual modality and (2) takes already effect at early automatic processing stages. Here, we addressed these questions by studying visual perception of socially meaningful stimuli in healthy individuals with varying degrees of psychosis proneness (n = 39). In a first task, we quantified participants’ prior for detecting faces in visual noise using a Bayesian decision model. In a second task, we measured participants’ prior for detecting direct gaze stimuli that were rendered invisible by continuous flash suppression. We found that the prior for detecting faces in noise correlated with hallucination proneness (r = 0.50, p = 0.001, Bayes factor 1/20.1) as well as delusion proneness (r = 0.46, p = 0.003, BF 1/9.4). The prior for detecting invisible direct gaze was significantly associated with hallucination proneness (r = 0.43, p = 0.009, BF 1/3.8) but not conclusively with delusion proneness (r = 0.30, p = 0.079, BF 1.7). Our results provide evidence for the idea that overly strong high-level priors for automatically detecting socially meaningful stimuli might constitute a processing alteration in psychosis.

Attentional bias towards negative stimuli in healthy individuals and the effects of trait anxiety

This study aimed to investigate the time course of attentional bias for negative information in healthy individuals and to assess the associated influence of trait anxiety. Thirty-eight healthy volunteers performed an emotional dot-probe task with pairs of negative and neutral scenes, presented for either 1 or 2 s and followed by a target placed at the previous location of either negative or neutral stimulus. Analyses included eye movements during the presentation of the scenes and response times associated with target localization. In a second step, analyses focused on the influence of trait anxiety. While there was no significant difference at the behavioral level, the eye-tracking data revealed that negative information held longer attention than neutral stimuli once fixated. This initial maintenance bias towards negative pictures then increased with increasing trait anxiety. However, at later processing stages, only individuals with the highest trait anxiety appeared to fixate longer on negative pictures than neutral pictures, individuals with low trait anxiety showing the opposite pattern. This study provides novel evidence that healthy individuals display an attentional maintenance bias towards negative stimuli, which is associated with trait anxiety.

Selective attentional bias to food-related stimuli in healthy individuals with characteristics towards orthorexia nervosa

PurposeIt has been argued that orthorexia nervosa (ON) is a unique type of disordered eating of food considered by the individual to be healthy. Given that in other eating disorder populations attentional preference for food-related cues influences eating behaviours, is it also likely that these biases may be a characteristic of ON tendency.MethodsEighty healthy individuals completed the ORTO-15 questionnaire (ON tendency), a modified Stroop task containing words related to healthy and unhealthy foods and perceived hunger levels pre- and post-testing. The ORTO-15 was used to identify participants within this sample who demonstrated more or less of the characteristics of ON.ResultsResults suggest that the presence of attentional bias to healthy, but not for unhealthy food-related stimuli independently predict increased ON tendency. Increased attentional bias towards healthy food-related stimuli is associated with increased scores on the ORTO-15.ConclusionAttentional bias, as a deficit in information processing, towards healthy food-related stimuli accounts for variability in ON characteristics.Level of evidenceLevel I, experimental study.

Interpretation bias in the face of pain: a discriminatory fear conditioning approach.

Background and aims Interpreting pain- and illness-related stimuli as health-threatening is common among chronic pain patients but also occurs in the general population. As interpretation bias (IB) may affect pain perception and might even play part in the development and maintenance of chronic pain, it is important to improve our understanding of this concept. Several studies suggest an association between IB and pain-related anxiety. However, those studies often rely on verbal and pictorial IB tasks that do not entail a threat of actual pain, therefore lacking personal relevance for healthy participants. The current study investigated whether healthy individuals show an IB towards ambiguous health-related stimuli in a context of actual pain threat, and explored whether this bias is associated to pain anxiety constructs. Methods Thirty-six healthy participants were conditioned to expect painful electrocutaneous shocks (unconditioned stimulus - US) after health-threat words (CS+) but not after neutral (non-health-threat) words (CS-) in order to establish fear of pain. Subsequently, they completed a verbal interpretation task that contained new CS+ and CS- stimuli as well as ambiguous non-reinforced health-threat and non-health-threat words. IB was assessed through shock expectancy ratings and startle responses to ambiguous and evident health threatening or neutral word stimuli. Pain-related anxiety was measured with validated questionnaires. Results The results show a general IB towards ambiguous health-related words on pain expectancies but not on startle response. An exploratory analysis suggests that this effect exists irrespective of pain-related anxiety levels which however may be due to a lack of power. Conclusion We present a novel experimental paradigm employing actual health threat that captures IB towards health-related stimuli in healthy individuals. Taken together, results provide evidence for the further consideration of IB as a latent vulnerability factor in the onset and maintenance of pain chronicity. In contrast to previous studies employing a safe, pain-free context, we found that healthy participants show an IB towards ambiguous health-related stimuli, when confronted with pain threat. Implications Like chronic pain patients, healthy individuals display an IB towards health-threat stimuli when these stimuli become personally relevant by carrying information about pending health threat. Therefore, the presented paradigm could be valuable for pain-related cognitive bias research in healthy participants as it may have a higher ecological validity than previous study designs. Future studies will have to elucidate the influence of anxiety constructs on IB in larger samples.

Effects of Anodal Transcranial Direct Current Stimulation on Somatosensory Recovery After Stroke

The aim of this study was to evaluate the effect of anodal transcranial direct current stimulation over the primary somatosensory cortex on the recovery of somatosensation, motor function, and the activities of daily living in patients with subacute stroke. This study was a prospective, randomized sham controlled, double-blinded study. Patients with subacute stroke having somatosensory deficits (N = 24) were enrolled and assigned randomly to the anodal and sham stimulation groups. Patients received 10 consecutive anodal or sham transcranial direct current stimulations over the primary somatosensory cortex on the side of the stroke lesion. Before and after each stimulation session, Nottingham sensory assessments, Semmes Weinstein monofilaments examination, and manual function tests were performed, and modified Brunnstrom classification, modified Barthel index, and functional ambulation categories were assessed. Although there was no clear significant difference between the two groups, when the changes from baseline to posttreatment evaluation were compared between the groups, a partially significant improvement was observed in the anodal stimulation group compared with the sham stimulation group. Interestingly, the tactile sensation of the unaffected side also improved. Moreover, the greater improvement in activities of daily living function was observed in the anodal stimulation group too. Anodal transcranial direct current stimulation over the primary somatosensory cortex may be a useful adjuvant therapy for the recovery of somatosensation and activities of daily living function in patients with sensory deficits after stroke.

Refuting the myth of non-response to exercise training: 'non-responders' do respond to higher dose of training.

The prevalence of cardiorespiratory fitness (CRF) non-response gradually declines in healthy individuals exercising 60, 120, 180, 240 or 300min per week for 6weeks. Following a successive identical 6-week training period but comprising 120min of additional exercise per week, CRF non-response is universally abolished. The magnitude of CRF improvement is primarily attributed to changes in haemoglobin mass. The potential for CRF improvement may be present and unveiled with appropriate exercise training stimuli in healthy individuals without exception. One in five adults following physical activity guidelines are reported to not demonstrate any improvement in cardiorespiratory fitness (CRF). Herein, we sought to establish whether CRF non-response to exercise training is dose-dependent, using a between- and within-subject study design. Seventy-eight healthy adults were divided into five groups (1-5) respectively comprising one, two, three, four and five 60min exercise sessions per week but otherwise following an identical 6-week endurance training (ET) programme. Non-response was defined as any change in CRF, determined by maximal incremental exercise power output (Wmax ), within the typical error of measurement (±3.96%). Participants classified as non-responders after the ET intervention completed a successive 6-week ET period including two additional exercise sessions per week. Maximal oxygen consumption (V̇O2 max ), haematology and muscle biopsies were assessed prior to and after each ET period. After the first ET period, Wmax increased (P<0.05) in groups 2, 3, 4 and 5, but not 1. In groups 1, 2, 3, 4 and 5, 69%, 40%, 29%, 0% and 0% of individuals, respectively, were non-responders. After the second ET period, non-response was eliminated in all individuals. The change in V̇O2 max with exercise training independently determined Wmax response (partial correlation coefficient, rpartial ≥0.74, P<0.001). In turn, total haemoglobin mass was the strongest independent determinant of V̇O2 max (rpartial =0.49, P<0.001). In conclusion, individual CRF non-response to exercise training is abolished by increasing the dose of exercise and primarily a function of haematological adaptations in oxygen-carrying capacity.

Being Anxious, Thinking Positively: The Effect of Emotional Context on Respiratory Sensory Gating.

Respiratory sensory gating function has been found decreased by induced negative emotion in healthy adults. The increased ratio of the respiratory-related evoked potential (RREP) N1 peak amplitude for the second occlusion (S2) vs. the first occlusion (S1), S2/S1, is indicative of such decreased respiratory sensory gating. In this study, we tested the hypothesis that a positive emotional context would enhance respiratory sensory gating function in healthy individuals. In addition, we tested the modulating role of individual anxiety levels. We compared respiratory sensory gating in 40 healthy individuals by the paired inspiratory occlusion paradigm in a positive and neutral emotional context induced by emotional picture viewing. The results showed that the group averaged RREP N1 peak amplitudes S2/S1 ratios were significantly smaller in the positive compared to neutral context (0.49 vs. 0.64; p < 0.01). Further, analysis showed that the ratio decrease was due to a reduced response to the S2 and an enhanced response to S1 in the positive emotional context (p < 0.05). The subgroup analyses showed that in the positive emotional context, both individuals with low-moderate anxiety levels and those with no anxiety demonstrated a significant decrease of their S2/S1 ratio, but only those with low-moderate anxiety levels showed reduced S2 amplitudes compared to the neutral context (p < 0.01). In conclusion, our results suggest that a positive emotional context is related to better brain inhibitory mechanisms by filtering out repetitive respiratory stimuli in healthy individuals, especially in the presence of low-moderate anxiety levels. Further, investigation on how positive emotional contexts might contribute to improved respiratory sensory gating ability in clinical populations is necessary.

Chronic Neuropathic Pain: It's about the Rhythm.

The neural mechanisms underlying the development and maintenance of chronic neuropathic pain remain unclear. Evidence from human investigations suggests that neuropathic pain is associated with altered thalamic burst firing and thalamocortical dysrhythmia. Additionally, experimental animal investigations show that neuropathic pain is associated with altered infra-slow (<0.1 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus. The aim of this investigation was to determine whether, in humans, neuropathic pain was also associated with altered infra-slow oscillations within the ascending "pain" pathway. Using resting-state functional magnetic resonance imaging, we found that individuals with orofacial neuropathic pain have increased infra-slow oscillatory activity throughout the ascending pain pathway, including within the spinal trigeminal nucleus, somatosensory thalamus, thalamic reticular nucleus, and primary somatosensory cortex. Furthermore, these infra-slow oscillations were temporally coupled across these multiple sites and occurred at frequencies similar to calcium waves in activated astrocytes. The region encompassing the spinal trigeminal nucleus also displayed increased regional homogeneity, consistent with a local spread of neural activity by astrocyte activation. In contrast, no increase in oscillatory behavior within the ascending pain pathway occurred during acute noxious stimuli in healthy individuals. These data reveal increased oscillatory activity within the ascending pain pathway that likely underpins increased thalamocortical oscillatory activity, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain. Significance statement: Chronic neuropathic pain is associated with altered thalamic firing and thalamocortical dysrhythmia. The mechanisms responsible for these changes remain unknown. In this study, we report in individuals with neuropathic pain increased oscillatory neural activity within the ascending pain pathway with evidence that these changes result from altered neural-astrocyte coupling. We propose a series of neural and glial events after nerve injury that result in the generation of altered thalamocortical activity and a persistent neuropathic pain state. Defining the underlying mechanisms responsible for neuropathic pain is critical if we are to develop more effective treatment regimens.

Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users.

Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal cortex in response to biologically salient stimuli in an emotional face matching task (EFMT). Amygdala activity and amygdala connectivity during the EFMT were assessed in 51 cocaine using males and 32 non-drug-using healthy males using functional magnetic resonance imaging (fMRI). Within the cocaine use group, we explored whether amygdala activation was associated with age of first use of cocaine and duration of cocaine use to distinguish between amygdala activation alterations as a cause or a consequence of cocaine use. We observed hyperactivity of the amygdala, thalamus, and hippocampus and reduced amygdala connectivity with the anterior cingulate gyrus in response to angry and fearful facial expressions in current cocaine users compared to controls. Increased amygdala activation was independently associated with earlier age of first cocaine use and with longer exposure to cocaine. Our findings suggest that amygdala hyperactivity to biologically salient stimuli may represent a risk factor for an early onset of cocaine use and that prolonged cocaine use may further sensitize amygdala activation. High amygdala activation to emotional face processing in current cocaine users may result from low prefrontal control of the amygdala response to such stimuli.

(326) Classification of brain activity response to painful heat stimuli in fibromyalgia patients and healthy controls

Hypersensitivity and other alterations in sensory processing occur in patients suffering from fibromyalgia syndrome, although the exact nature of how sensory processing contributes to these differences remains unclear. Investigating differences in acute pain processing in fibromyalgia could potentially help uncover mechanisms by which chronic pain processing is modified in fibromyalgia patients. Our recent study used a multivariate approach to demonstrate that brain activity can be used to validate various levels of painful and non-painful heat stimuli in healthy individuals.1 Our goal here was to extend this approach to classify levels of painful heat stimuli in a chronic pain population. Subjects (10 healthy controls, 9 fibromyalgia patients) completed a quantitative sensory testing (QST) session to determine individualized temperatures evoking pain levels of 5 and 7 (visual analog scale, VAS, 0-10). Functional MRI scans and VAS pain ratings were collected while subjects underwent painful heat stimuli on their lower right leg, using individualized temperatures to match heat pain levels across patients and healthy controls. Our preliminary conventional analyses show significant differences in brain activity in response to moderate (VAS pain level 5) and high (VAS pain level 7) levels of heat pain across all subjects. Further analyses will aim to use a multivariate approach (support vector machine, SVM) to classify levels of painful heat stimuli and distinguish between brain activity evoked by acute pain in fibromyalgia patients versus in healthy controls. Our future goal is to identify a signature pattern of brain activity response to acute heat pain that is able to differentiate between fibromyalgia patients and healthy controls. (1. Brown, J.E., et al., Towards a physiology-based measure of pain: patterns of human brain activity distinguish painful from non-painful thermal stimulation. PLoS One, 2011. 6(9): p. e24124.)

Temporal discrimination, a cervical dystonia endophenotype: penetrance and functional correlates.

The pathogenesis of adult-onset primary dystonia remains poorly understood. There is variable age-related and gender-related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)-the shortest time interval at which two separate stimuli can be detected as being asynchronous-is abnormal both in patients with cervical dystonia and in their unaffected first-degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age-related and gender-related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first-degree relatives of 84 patients with cervical dystonia. In 24 unaffected first-degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits.

The adaptive threat bias in anxiety: Amygdala–dorsomedial prefrontal cortex coupling and aversive amplification

Functionally, anxiety serves to increase vigilance towards aversive stimuli and improve the ability to detect and avoid danger. We have recently shown, for instance, that anxiety increases the ability to a) detect and b) instigate defensive responses towards aversive and not appetitive face stimuli in healthy individuals. This is arguably the key adaptive function of anxiety, yet the neural circuitry underlying this valence-specific effect is unknown. In the present translational study, we sought evidence for the proposition that dorsomedial regions of the prefrontal (DMPFC) and cingulate cortex constitute the human homologue of the rodent prelimbic and are thus associated with increased amygdala responding during this adaptive threat bias in anxiety. To this end, we applied a novel functional connectivity analysis to healthy subjects (N=20) identifying the emotion of fearful and happy faces in an fMRI scanner under anxious (threat of unpredictable foot shock) and non-anxious (safe) conditions. We showed that anxiety significantly increased positive DMPFC-amygdala connectivity during the processing of fearful faces. This effect was a) valence-specific (it was not seen for happy faces), b) paralleled by faster behavioral response to fearful faces, and c) correlated positively with trait anxiety. As such we provide the first experimental support for an anxiety-mediated, valence-specific, DMPFC-amygdala aversive amplification mechanism in healthy humans. This may be homologous to the rodent prelimbic-amygdala circuit and may, given the relationship with trait anxiety, underlie vulnerability to anxiety disorders. This study thus pinpoints a key neural mechanism in adaptive anxiety and highlights its potential link to maladaptive anxiety.

Prediction of Experimental Pain Sensitivity by Attention to Pain-Related Stimuli in Healthy Individuals

The aim of the present study was to assess the predictive power of the processing of pain-related information, comprising concepts of hypervigilance to pain, pain catastrophizing, and pain-related anxiety (questionnaires) as well as attentional processes related to pain-related stimuli (dot-probe task) in explaining individual differences in experimental pain sensitivity (pressure/thermal pain threshold). In 160 healthy participants (ages 13-61; 80 females), results of hierarchical multiple regression analyses showed that self-reported hypervigilance contributed significantly to the prediction of pain sensitivity, whereas pain catastrophizing and anxiety did not. However, inconsistent with prediction, the effect was in the opposite direction, indicating that vigilance to pain sensations or stimuli is associated with lower pain sensitivity in healthy individuals. Entering the attentional bias indices from the dot-probe task showed that an increased bias to pain words is related to higher experimental pain sensitivity, which confirms the hypothesis.

Association between exercise hemodynamics and changes in local vascular function following acute exercise

Skeletal muscle contractions are associated with physical stimuli that act upon muscle vasculature, including increased shear stress and blood pressure. It is unclear if acute dynamic exercise alters local vascular function. The purpose of this study was to examine the role of exercise hemodynamics on the effects of acute exercise on vascular function, as evaluated by brachial artery flow-mediated dilation (FMD). Healthy individuals (n = 14; age, 18-34years) performed 30min of handgrip exercise at fast and slow contractions. Blood pressure during exercise was measured using a Vasotrac system (Medwave Inc.), while shear rate during exercise and FMD at rest and after 30min of recovery from exercise were measured in the brachial artery of the active arm using Doppler ultrasound. Estimated contractile work was correlated with blood pressure (r = 0.61, p< 0.01) and retrograde shear rate (r =-0.78, p< 0.01). As a result, blood pressure was higher (p< 0.05) and oscillatory shear index was lower (p< 0.05) during slow as compared with fast contractions. On average, FMD was unchanged following fast contractions (5.4± 3.4%dilation to 6.1± 3.8%dilation; p = 0.19), but significantly reduced following slow contractions (6.9± 4.2%dilation to 3.6± 2.5%dilation; p = 0.01). Within slow contractions, subgroup analysis revealed blood pressure to associate with the change in FMD; such that individuals with mean blood pressure>100mm Hg (range, 102-139mm Hg) during exercise had larger decreases in FMD than individuals with lower exercise blood pressure. These results indicate that impaired local vascular function following acute exercise with high contractile activity is associated with blood pressure stimuli in healthy individuals.

Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

COMT genetic variation affects fear processing: Psychophysiological evidence.

Emotional dysregulation is a core characteristic of many psychiatric diseases, including the anxiety disorders. Although heritable influences account for a significant degree of variation in risk for such disorders, relatively few candidate susceptibility factors have been identified. A coding variant in one such gene, encoding the dopamine catabolic enzyme catechol-O-methyltransferase (COMT Val158Met), has previously been associated with anxiety and with anxiety-related temperament and altered neural responses to affective stimuli in healthy individuals. In 96 healthy women recruited from a sample of 800 participants according to genotype, the authors tested for an association between the DRD2/ANKK1 Taq Ia, the COMT Val158Met, and a psychophysiological measure of emotion processing, the acoustic affective startle reflex modulation (ASRM) paradigm, and found that COMT genotype significantly affected startle reflex modulation by aversive stimuli, with Met158 homozygotes exhibiting a markedly potentiated startle reflex compared with Val158 carriers. A trait measure of anxiety (Gray's Behavioral Inhibition System; J. A. Gray & N. McNaughton, 2000) was also associated with ASRM. The functional polymorphism in the dopamine D2 receptor (DRD2/ANKK1 Taq Ia) had no effect on startle modulation. The findings support prior genetic and neuroimaging associations of the COMT 158Met allele to affective psychopathology and alterations in neural systems for emotional arousal and regulation.

Pedophilia is Linked to Reduced Activation in Hypothalamus and Lateral Prefrontal Cortex During Visual Erotic Stimulation

Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.