Brain Responses to Hypnotic Verbal Suggestions Predict Pain Modulation

Background: The effectiveness of hypnosis in reducing pain is well supported by the scientific literature. Hypnosis typically involves verbal suggestions but the mechanisms by which verbal contents are transformed into predictive signals to modulate perceptual processes remain unclear. We hypothesized that brain activity during verbal suggestions would predict the modulation of responses to acute nociceptive stimuli.Methods: Brain activity was measured using BOLD-fMRI in healthy participants while they listened to verbal suggestions of HYPERALGESIA, HYPOALGESIA, or NORMAL sensation (control) following a standardized hypnosis induction. Immediately after the suggestions, series of noxious electrical stimuli were administered to assess pain-related responses. Brain responses measured during the suggestions were then used to predict changes in pain-related responses using delayed regression analyses.Results: Listening to suggestions of HYPERALGESIA and HYPOALGESIA produced BOLD decreases (vs. control) in the parietal operculum (PO) and in the anterior midcingulate cortex (aMCC), and increases in the left parahippocampal gyrus (lPHG). Changes in activity in PO, aMCC and PHG during the suggestions predicted larger pain-evoked responses following the HYPERALGESIA suggestions in the anterior cingulate cortex (ACC) and the anterior insula (aINS), and smaller pain-evoked responses following the HYPOALGESIA suggestions in the ACC, aMCC, posterior insula (pINS) and thalamus. These changes in pain-evoked brain responses are consistent with the changes in pain perception reported by the participants in HYPERALGESIA and HYPOALGESIA, respectively.Conclusions: The fronto-parietal network (supracallosal ACC and PO) has been associated with self-regulation and perceived self-agency. Deactivation of these regions during suggestions is predictive of the modulation of brain responses to noxious stimuli in areas previously associated with pain perception and pain modulation. The response of the hippocampal complex may reflect its role in contextual learning, memory and pain anticipation/expectations induced by verbal suggestions of pain modulation. This study provides a basis to further explore the transformation of verbal suggestions into perceptual modulatory processes fundamental to hypnosis neurophenomenology. These findings are discussed in relation to predictive coding models.

Give me a pain that I am used to: distinct habituation patterns to painful and non-painful stimulation

Pain habituation is associated with a decrease of activation in brain areas related to pain perception. However, little is known about the specificity of these decreases to pain, as habituation has also been described for other responses like spinal reflexes and other sensory responses. Thus, it might be hypothesized that previously reported reductions in activation are not specifically related to pain habituation. For this reason, we performed a 3 T fMRI study using either painful or non-painful electrical stimulation via an electrode attached to the back of the left hand. Contrasting painful vs. non-painful stimulation revealed significant activation clusters in regions well-known to be related to pain processing, such as bilateral anterior and posterior insula, primary/secondary sensory cortices (S1/S2) and anterior midcingulate cortex (aMCC). Importantly, our results show distinct habituation patterns for painful (in aMCC) and non-painful (contralateral claustrum) stimulation, while similar habituation for both types of stimulation was identified in bilateral inferior frontal gyrus (IFG) and contralateral S2. Our findings thus distinguish a general habituation in somatosensory processing (S2) and reduced attention (IFG) from specific pain and non-pain related habituation effects where pain-specific habituation effects within the aMCC highlight a change in affective pain perception.

Empathy concerns enhance prosociality and modulate frontal theta oscillatory activity in young adults

Decision making is a process that can be strongly affected by social factors. Profuse evidence has shown how people deviate from traditional rational-choice predictions under different levels of social interactions. The emergence of prosocial decision making, defined as any action that is addressed to benefit another individual even at the expense of personal benefits, has been reported as an important example of such social influence. Furthermore, brain evidence has shown the involvement of structures such the prefrontal cortex, anterior insula and midcingulate cortex during decision settings in which a decision maker interacts with others under physical pain or distress or while being observed by others. Using a slightly modified version of the dictator game, we tested the hypothesis that the inclusion of another person into the decision setting increases prosocial decisions in young adults and that this increase is higher when the other person is associated with others in need. At the brain level, we hypothesized that the increase in prosocial decisions correlates with frontal theta activity as a marker of empathy saliency. The results showed that the inclusion of another person into the decision setting increased prosocial behavior only when this presence was associated with someone in need and that this was associated with an increase in frontocentral theta-oscillatory activity. These results suggest that the presence of someone in need enhances both empathy concerns and norm compliance, raising the participants’ prosocial decision making.

μ-opioid receptor availability is associated with sex drive in human males

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. We measured healthy male subjects’ (n = 52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n = 108) of anatomical MR images provided limited evidence for positive association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

Impaired self-awareness of cognitive deficits in Parkinson's disease relates to cingulate cortex dysfunction

Background Impaired self-awareness of cognitive deficits (ISAcog) has rarely been investigated in Parkinson's disease (PD). ISAcog is associated with poorer long-term outcome in other diseases. This study examines ISAcog in PD with and without mild cognitive impairment (PD-MCI), compared to healthy controls, and its clinical-behavioral and neuroimaging correlates. Methods We examined 63 PD patients and 30 age- and education-matched healthy controls. Cognitive state was examined following the Movement Disorder Society Level II criteria. ISAcog was determined by subtracting z-scores (based on controls' scores) of objective tests and subjective questionnaires. Neural correlates were assessed by structural magnetic resonance imaging (MRI) and 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) in 47 patients (43 with MRI) and 11 controls. We analyzed whole-brain glucose metabolism and cortical thickness in regions where FDG-uptake correlated with ISAcog. Results PD-MCI patients (N = 23) showed significantly more ISAcog than controls and patients without MCI (N = 40). When all patients who underwent FDG-PET were examined, metabolism in the bilateral superior medial frontal gyrus, anterior and midcingulate cortex negatively correlated with ISAcog (FWE-corrected p < 0.001). In PD-MCI, ISAcog was related to decreased metabolism in the right superior temporal lobe and insula (N = 13; FWE-corrected p = 0.023) as well as the midcingulate cortex (FWE-corrected p = 0.002). Cortical thickness was not associated with ISAcog in these regions. No significant correlations were found between ISAcog and glucose metabolism in controls and patients without MCI. Conclusions Similar to Alzheimer's disease, the cingulate cortex seems to be relevant in ISAcog in PD. In PD-MCI patients, ISAcog might result from a disrupted network that regulates awareness of cognition and error processes.

Prediction and action in cortical pain processing

Predicting that a stimulus is painful facilitates action to avoid harm. But does the prediction of upcoming painful events engage the same or different processes than acting to avoid or reduce current pain? In this fMRI experiment, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, and the ability of voluntary action to affect the duration of the upcoming stimulation. Participants (n = 30) performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Participants’ task was to press a response button within a short time window upon the presentation of a response cue during S1. On action-effective trials, pressing the button within the specified time window reduced the duration of the upcoming stimulation. On action-ineffective trials, pressing the button had no effect on upcoming stimulation. Predicted pain increased activation in regions including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Region-of-interest analyses revealed that insula’s responses for predicted pain were also modulated by potential action consequences, especially in the left hemisphere, albeit without a direct relationship with motor output. Taken together, these findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead depends on the consequences of that stimulus for sensorimotor control of behavior.Significance statementDuring acute pain, the processing of an acute sensory event likely occurs in parallel with predictive processing about its relevance for current and upcoming voluntary behavior. Here, we temporally separated the functional processes underlying current and predicted pain and found that activation in regions typically implicated in acute pain is modulated both by the noxious nature of upcoming events, as well as by the possibility to affect those events via voluntary action. Specifically, activation in anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula during the delivery of a painful or nonpainful stimulus was modulated by whether an upcoming stimulus would be painful. Furthermore, ACC/MCC involvement in pain prediction depended on whether a meaningful action was performed, i.e., whether a button-press action would reduce the duration of the upcoming stimulus. Although insula activation was also affected by the possibility of the button-press action to reduce the duration of the upcoming stimulation, only MCC had a direct relationship with motor output.

Whole-brain morphological alterations associated with trigeminal neuralgia

Background Novel neuroimaging strategies have the potential to offer new insights into the mechanistic basis for trigeminal neuralgia (TN). The present study aims to conduct whole-brain morphometry analyses of TN patients and to assess the value of group-level neocortical and subcortical structural patterns as tools for diagnostic biomarker exploration. Methods Cortical thickness, surface area, and myelin levels in the neocortex were measured via magnetic resonance imaging (MRI). The radial distance and the Jacobian determinant of the subcortex in 43 TN patients and 43 matched controls were compared. Pattern learning algorithms were employed to establish the utility of group-level MRI findings as tools for predicting TN. An additional 40 control patients with hemifacial spasms were then evaluated to assess algorithm sensitivity and specificity. Results TN patients exhibited reductions in cortical indices in the anterior cingulate cortex (ACC), the midcingulate cortex (MCC), and the posterior cingulate cortex (PCC) relative to controls. They further presented with widespread subcortical volume reduction that was most evident in the putamen, the thalamus, the accumbens, the pallidum, and the hippocampus. Whole brain-level morphological alterations successfully enable automated TN diagnosis with high specificity (TN: 95.35 %; disease controls: 46.51 %). Conclusions TN is associated with a distinctive whole-brain structural neuroimaging pattern, underscoring the value of machine learning as an approach to differentiating between morphological phenotypes, ultimately revealing the full spectrum of this disease and highlighting relevant diagnostic biomarkers.

Reading and Calculation Neural Systems and Their Weighted Adaptive Use for Programming Skills

Software programming is a modern activity that poses strong challenges to the human brain. The neural mechanisms that support this novel cognitive faculty are still unknown. On the other hand, reading and calculation abilities represent slightly less recent human activities, in which neural correlates are relatively well understood. We hypothesize that calculus and reading brain networks provide joint underpinnings with distinctly weighted contributions which concern programming tasks, in particular concerning error identification. Based on a meta-analysis of the core regions involved in both reading and math and recent experimental evidence on the neural basis of programming tasks, we provide a theoretical account that integrates the role of these networks in program understanding. In this connectivity-based framework, error-monitoring processing regions in the frontal cortex influence the insula, which is a pivotal hub within the salience network, leading into efficient causal modulation of parietal networks involved in reading and mathematical operations. The core role of the anterior insula and anterior midcingulate cortex is illuminated by their relation to performance in error processing and novelty. The larger similarity that we observed between the networks underlying calculus and programming skills does not exclude a more limited but clear overlap with the reading network, albeit with differences in hemispheric lateralization when compared with prose reading. Future work should further elucidate whether other features of computer program understanding also use distinct weights of phylogenetically “older systems” for this recent human activity, based on the adjusting influence of fronto-insular networks. By unraveling the neural correlates of program understanding and bug detection, this work provides a framework to understand error monitoring in this novel complex faculty.