Neural underpinnings of preferential pain learning and the modulatory role of fear

Due to its unique biological relevance, pain-related learning might differ from learning from other aversive experiences. This functional magnetic resonance imaging study compared neural mechanisms underlying the acquisition and extinction of different threats in healthy humans. We investigated whether cue-pain associations are acquired faster and extinguished slower than cue associations with an equally unpleasant tone. Additionally, we studied the modulatory role of stimulus-related fear. Therefore, we used a differential conditioning paradigm, in which somatic heat pain stimuli and unpleasantness-matched auditory stimuli served as US. Our results show stronger acquisition learning for pain- than tone-predicting cues, which was augmented in participants with relatively higher levels of fear of pain. These behavioral findings were paralleled by activation of brain regions implicated in threat processing (insula, amygdala) and personal significance (ventromedial prefrontal cortex). By contrast, extinction learning seemed to be less dependent on the threat value of the US, both on the behavioral and neural levels. Amygdala activity, however, scaled with pain-related fear during extinction learning. Our findings on faster and stronger (i.e. “preferential”) pain learning and the role of fear of pain are consistent with the biological relevance of pain and may be relevant to the development or maintenance of chronic pain

A suicide attentional bias as implicit cognitive marker of suicide vulnerability in a high-risk sample.

INTRODUCTION Suicide risk assessment based on self-report questionnaires is considered as problematic because risk states are dynamic and at-risk individuals may conceal suicidal intentions for several reasons. Therefore, recent research efforts increasingly focus on implicit risk markers such as the suicide attentional bias (SAB) measured with the Suicide Stroop Task (SST). However, most SST studies failed to demonstrate a SAB in individuals with suicide risk and repeatedly demonstrated insufficient psychometrics of the SST. This study aimed to investigate a SAB using a modified SST (M-SST) and to test its psychometric properties. METHOD We compared n = 61 healthy controls and a high-risk inpatient sample of n = 40 suicide ideators and n = 40 suicide attempters regarding interference scores of positive, negative and suicide-related words. Interference scores were calculated by subtracting the mean reaction time (mean RT) of the neutral words from the mean RT of the suicide-related words (mean RT Suicide -mean RT Neutral), resulting in a suicide-specific interference score. Similarly, interference scores were calculated for the positive and negative words by subtracting the mean RT of neutral words from the mean RT of positive and negative words. RESULTS A Group × Interference ANOVA showed a significant interaction effect (p <.001, ηp2 = .09), indicating that group effects significantly vary across interference type. Post hoc comparisons revealed that both ideators and attempters demonstrated greater interferences only for suicide-related words compared to healthy controls, indicating a SAB in patients, while a difference between ideators and attempters was lacking. The suicide interference score classified with an AUC = 0.73, 95% CI [0.65 - 0.82], p <.001, between controls and patients with STBs. The M-SST demonstrated good internal consistency and convergent validity. DISCUSSION The study adds evidence to the assumptions of the Cognitive Model of Suicide, viewing a SAB as a cognitive marker of suicide vulnerability independently of the engagement in suicidal behavior. The results' clinical implications are discussed in the context of recommended intervention strategies during an acute suicidal state. Future studies with the M-SST should include non-suicidal patient controls to investigate whether a SAB is uniquely related to suicidality

Implicit measures of suicide vulnerability: Investigating suicide-related information-processing biases and a deficit in behavioral impulse control in a high-risk sample and healthy controls.

OBJECTIVE Relevant implicit markers of suicidal thoughts and behaviors (STBs) have only been studied in isolation with mixed evidence. This is the first study that investigated a suicide attentional bias, a death-identity bias and a deficit in behavioral impulsivity in a high-risk sample and healthy controls. METHOD We administered the Death Implicit Association Test, the Modified Suicide Stroop Task, and a Go/No-Go Task to inpatient suicide ideators (n = 42), suicide attempters (n = 40), and community controls (n = 61). RESULTS Suicide ideators and attempters showed a suicide attentional bias and a death-identity bias compared to healthy controls. Ideators and attempters did not differ in these implicit information-processing biases. Notably, only attempters were more behaviorally impulsive compared to controls; however, ideators and attempters did not significantly differ in behavioral impulsivity. Moreover, implicit scores were positively intercorrelated in the total sample. CONCLUSION In line with the Cognitive Model of Suicide, ideators and attempters display suicide-related information processing biases, which can be considered as implicit cognitive markers of suicide vulnerability. Furthermore, attempters have elevated levels of behavioral impulsiveness. These results are highly relevant in the context of crisis intervention strategies and warrant further research

Enhanced pain-related conditioning for face compared to hand pain.

Pain is evolutionarily hardwired to signal potential danger and threat. It has been proposed that altered pain-related associative learning processes, i.e., emotional or fear conditioning, might contribute to the development and maintenance of chronic pain. Pain in or near the face plays a special role in pain perception and processing, especially with regard to increased pain-related fear and unpleasantness. However, differences in pain-related learning mechanisms between the face and other body parts have not yet been investigated. Here, we examined body-site specific differences in associative emotional conditioning using electrical stimuli applied to the face and the hand. Acquisition, extinction, and reinstatement of cue-pain associations were assessed in a 2-day emotional conditioning paradigm using a within-subject design. Data of 34 healthy subjects revealed higher fear of face pain as compared to hand pain. During acquisition, face pain (as compared to hand pain) led to a steeper increase in pain-related negative emotions in response to conditioned stimuli (CS) as assessed using valence ratings. While no significant differences between both conditions were observed during the extinction phase, a reinstatement effect for face but not for hand pain was revealed on the descriptive level and contingency awareness was higher for face pain compared to hand pain. Our results indicate a stronger propensity to acquire cue-pain-associations for face compared to hand pain, which might also be reinstated more easily. These differences in learning and resultant pain-related emotions might play an important role in the chronification and high prevalence of chronic facial pain and stress the evolutionary significance of pain in the head and face

Age-dependent decline of endogenous pain control: exploring the effect of expectation and depression.

Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20-40 years, middle-aged = 41-60 years, old = 61-80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age

A randomised-controlled trial to evaluate the app-based multimodal weight-loss program zanadio for patients with obesity

Objective Although the prevalence of obesity is constantly high, the care situation for patients with obesity is still insufficient. The advent of digital, evidence-based therapies to treat obesity could help alleviate this situation. This study therefore aimed at evaluating the effectiveness of the app-based, multimodal weight loss programme zanadio. Methods To examine the effectiveness for sustained weight loss of zanadio, a randomised-controlled trial (DRKS00024415) was conducted between January 2021 and March 2022. 150 adults with obesity were randomised into an intervention group or a control group. While the participants of the intervention group used zanadio for one year, participants in the control group were not allowed to use the app during the study period but were free to start other weight-loss attempts. The primary endpoint weight change (in %) and the secondary endpoints quality of life, well-being, and waist-to-height ratio, were assessed every three months (T0, T1, T2, T3, T4) via telephone interviews and online questionnaires. For the statistical analyses intention-to-treat and per-protocol analyses were performed. Results After 12 months, based on an intention-to-treat analysis, participants of the intervention group lost on average -7.75% (95% CI=[-9.66, -5.84]) of their initial body weight, while the control group showed no weight loss at the end of the study (M=0.00%, [-1.98, 1.99]). Importantly, the intervention group achieved a clinically relevant (< 5%) and significant weight reduction. These results were confirmed by a per-protocol analysis. Moreover, all secondary endpoints improved significantly in the intervention group, with significantly greater improvements in well-being and waist-to-height ratio than in the control group. Conclusion This study showed that adults with obesity who have used zanadio achieved a significant and clinically relevant weight loss within 12 months and further improved other obesity-related health variables compared to a wait-list control group. Limitations of the study are the mainly female sample and the exclusively self-reported outcome measures. Due to its effectiveness and flexible applicability, zanadio represents a low-threshold and widely accessible treatment offer for patients in Germany, that might alleviate the present care gap for patients with obesity.Peer reviewe

Phasic and Tonic Pain Differentially Impact the Interruptive Function of Pain

<div><p>The interruptive effect of painful experimental stimulation on cognitive processes is a well-known phenomenon. This study investigated the influence of pain duration on the negative effects of pain on cognition. Thirty-four healthy volunteers performed a rapid serial visual presentation task (RSVP) in which subjects had to detect (visual detection task) and count the occurrence of a target letter (working memory task) in two separate sessions while being stimulated on the left volar forearm with either short (2 sec) or long (18 sec) painful heat stimuli of equal subjective intensity. The results show that subjects performed significantly worse in the long pain session as indexed by decreased detection and counting performance. Interestingly, this effect on performance was also observed during control trials of the long pain session in which participants did not receive any painful stimulation. Moreover, subjects expected long painful stimulation to have a greater impact on their performance and individual expectation correlated with working memory performance. These findings suggest that not only the length of painful stimulation but also its expected ability to impair cognitive functioning might influence the interruptive function of pain. The exact relevance of expectation for the detrimental effects of pain on cognitive processes needs to be explored in more detail in future studies.</p></div

The effect of treatment history on therapeutic outcome: psychological and neurobiological underpinnings.

It is increasingly recognized that the efficacy of medical treatments is determined in critical part by the therapeutic context in which it is delivered. An important characteristic of that context is treatment history. We recently reported first evidence for a carry-over of treatment experience to subsequent treatment response across different treatment approaches. Here we expand on these findings by exploring the psychological and neurobiological underpinnings of the effect of treatment experience on future treatment response in an experimental model of placebo analgesia with a conditioning procedure. In a combined behavioral and neuroimaging study we experimentally induced positive or negative experiences with an analgesic treatment in two groups of healthy human subjects. Subsequently we compared responses to a second, different analgesic treatment between both groups. We found that participants with an experimentally induced negative experience with the first treatment showed a substantially reduced response to a second analgesic treatment. Intriguingly, several psychological trait variables including anxiety, depression and locus of control modulate the susceptibility for the effects of prior treatment experiences on future treatment outcome. These behavioral effects were supported by neuroimaging data which showed significant differences in brain regions encoding pain and analgesia between groups. These differences in activation patterns were present not only during the pain phase, but also already prior to painful stimulation and scaled with the individual treatment response. Our data provide behavioral and neurobiological evidence showing that the influence of treatment history transfers over time and over therapeutic approaches. Our experimental findings emphasize the careful consideration of treatment history and a strictly systematic treatment approach to avoid negative carry-over effects

An externally validated resting-state brain connectivity signature of pain-related learning

Pain can be conceptualized as a precision signal for reinforcement learning in the brain and alterations in these processes are a hallmark of chronic pain conditions. Investigating individual differences in pain-related learning therefore holds important clinical and translational relevance. Here, we developed and externally validated a novel resting-state brain connectivity-based predictive model of pain-related learning. The pre-registered external validation indicates that the proposed model explains 8-12% of the inter-individual variance in pain-related learning. Model predictions are driven by connections of the amygdala, posterior insula, sensorimotor, frontoparietal, and cerebellar regions, outlining a network commonly described in aversive learning and pain. We propose the resulting model as a robust and highly accessible biomarker candidate for clinical and translational pain research, with promising implications for personalized treatment approaches and with a high potential to advance our understanding of the neural mechanisms of pain-related learning

Task performance correlates with individual expectation.

<p>Correlation between the subjects’ expectation about the influence of pain on task performance and the actual performance difference in the counting task between painful and non-painful trials showing that the more subjects expect pain to disturb their performance the worse their short-term memory performance is under pain.</p