Effects of emotional valence and intensity on cognitive and affective empathy after insula lesions.

The insula plays a central role in empathy. However, the complex structure of cognitive (CE) and affective empathy (AE) deficits following insular damage is not fully understood. In the present study, patients with insular lesions (n = 20) and demographically matched healthy controls (n = 24) viewed ecologically valid videos that varied in terms of valence and emotional intensity. The videos showed a person (target) narrating a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions, they continuously rated their own affect. Mean squared error (MSE) assessed deviations between subject and target ratings. Patients differed from controls only in negative, low-intensity AE, rating their own affective state less negative than the target. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty pointing to a threshold role of the insula in online ratings of AE.

What you give is what you get: Payment of one randomly selected trial induces risk-aversion and decreases brain responses to monetary feedback.

In economic studies, it is standard practice to pay out the reward of only one randomly selected trial (pay-one) instead of the total reward accumulated across trials (pay-all), assuming that both methods are equivalent. We tested this assumption by recording electrophysiological activity to reward feedback from participants engaged in a decision-making task under both a pay-one and a pay-all condition. We show that participants are approximately 12% more risk averse in the pay-one condition than in the pay-all condition. Furthermore, we observed that the electrophysiological response to monetary rewards, the reward positivity, is significantly reduced in the pay-one condition relative to the pay-all condition. The difference of brain responses is associated with the difference in risky behavior across conditions. We concluded that the two payment methods lead to significantly different results and are therefore not equivalent.

Referred cramping phantom hand pain elicited in the face and eliminated by peripheral nerve block.

Phantom limb pain is a restricting condition for a substantial number of amputees with quite different characteristics of pain. Here, we report on a forearm amputee with constant phantom pain in the hand, in whom we could regularly elicit the rare phenomenon of referred cramping phantom pain by touching the face. To clarify the underlying mechanisms, we followed the cramp during the course of an axillary blockade of the brachial plexus. During the blockade, both phantom pain and the referred cramp were abolished, while a referred sensation of "being touched at the phantom" persisted. Furthermore, to identify the cortical substrate, we elicited the cramp during functional magnetic imaging. Imaging revealed that referred cramping phantom limb pain was associated with brain activation of the hand representation in the primary sensorimotor cortex. The results support the hypothesis that referred cramping phantom limb pain in this case is associated with a substantial brain activation in the hand area of the deafferented sensorimotor cortex. However, this alone is not sufficient to elicit referred cramping phantom limb pain. Peripheral inputs, both, from the arm nerves affected by the amputation and from the skin in the face at which the referred cramp is evoked, are a precondition for referred cramping phantom limb pain to occur, at least in this case.

The role of the cerebellum for feedback processing and behavioral switching in a reversal-learning task.

Previous studies have reported cerebellar activations during error and reward processing. The present study investigated if the cerebellum differentially processes feedback depending on changes in response strategy during reversal learning, as is conceivable given its internal models for movement and thought. Negative relative to positive feedback in an fMRI-based reversal learning task was hypothesized to be associated with increased cerebellar activations. Moreover, increased activations were expected for negative feedback followed by a change in response strategy compared to negative feedback not followed by such a change, and for first positive feedback after compared to final negative feedback before a change, due to updating of internal models. As predicted, activation in lobules VI and VIIa/Crus I was increased for negative relative to positive feedback, and for final negative feedback before a change in response strategy relative to negative feedback not associated with a change. Moreover, activation was increased for first positive feedback after relative to final negative feedback before a change. These findings are consistent with updating of cerebellar internal models to accommodate new behavioral strategies. Recruitment of posterior regions in reversal learning is in line with the cerebellar functional topography, with posterior regions involved in complex motor and cognitive functions.

Dermatomal Organization of SI Leg Representation in Humans: Revising the Somatosensory Homunculus.

Penfield and Rasmussen's homunculus is the valid map of the neural body representation of nearly each textbook of biology, physiology, and neuroscience. The somatosensory homunculus places the foot representation on the mesial surface of the postcentral gyrus followed by the representations of the lower leg and the thigh in superio-lateral direction. However, this strong homuncular organization contradicts the "dermatomal" organization of spinal nerves. We used somatosensory-evoked magnetic fields and source analysis to study the leg's neural representation in the primary somatosensory cortex (SI). We show that the representation of the back of the thigh is located inferior to the foot's representation in SI whereas the front of the thigh is located laterally to the foot's representation. This observation indicates that the localization of the leg in SI rather follows the dermatomal organization of spinal nerves than the typical map of neighboring body parts as depicted in Penfield and Rasmussen's illustration of the somatosensory homunculus.

Effects of Temporary Functional Deafferentation in Chronic Stroke Patients: Who Profits More?

Temporary functional deafferentation (TFD) by an anesthetic cream on the stroke-affected forearm was shown to improve sensorimotor abilities of stroke patients. The present study investigated different predictors for sensorimotor improvements during TFD and indicated outcome differences between patients grouped in subcortical lesions only and lesions with any cortical involvement. Thirty-four chronic stroke patients were temporarily deafferented on the more affected forearm by an anesthetic cream. Somatosensory performance was assessed using von Frey Hair and grating orientation task; motor performance was assessed by a shape-sorter-drum task. Seven potential predictors were entered into three linear multiple regression models. Furthermore, effects of TFD on outcome variables for the two groups (cortical versus subcortical lesion) were compared. Sex and sensory deficit were significant predictors for changes in motor function while age accounted for changes in grating orienting task. Males, patients with a stronger sensory deficit, and older patients profited more. None of the potential predictors made significant contributions to changes in threshold for touch. Furthermore, there were no differences in sensorimotor improvement between lesion site groups. The effects of TFD together with the low predictability of the investigated parameters suggest that characteristics of patients alone are not suitable to exclude some patients from TFD.

Look who's judging-Feedback source modulates brain activation to performance feedback in social anxiety.

It is as yet unknown if behavioral and neural correlates of performance monitoring in socially anxious individuals are affected by whether feedback is provided by a person or a computer. This fMRI study investigated modulation of feedback processing by feedback source (person vs. computer) in participants with high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a choice task in which they were informed that they would receive positive or negative feedback from a person or the computer. Subjective ratings indicated increased arousal and anxiety in HSA versus LSA, most pronounced for social and negative feedback. FMRI analyses yielded hyperactivation in ventral medial prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social relative to computer feedback, and in mPFC/ventral ACC for positive relative to negative feedback in HSA as compared to LSA. These activation patterns are consistent with increased interoception and self-referential processing in social anxiety, especially during processing of positive feedback. Increased ACC activation in HSA to positive feedback may link to unexpectedness of (social) praise as posited in social anxiety disorder (SAD) psychopathology. Activation in rostral ACC showed a reversed pattern, with decreased activation to positive feedback in HSA, possibly indicating altered action values depending on feedback source and valence. The present findings corroborate a crucial role of mPFC for performance monitoring in social anxiety.

Parametric modulation of reward sequences during a reversal task in ACC and VMPFC but not amygdala and striatum.

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE.

Aberrant network connectivity during error processing in patients with schizophrenia.

BACKGROUND: Neuroimaging methods have pointed to deficits in the interaction of large-scale brain networks in patients with schizophrenia. Abnormal connectivity of the right anterior insula (AI), a central hub of the salience network, is frequently reported and may underlie patients' deficits in adaptive salience processing and cognitive control. While most previous studies used resting state approaches, we examined right AI interactions in a task-based fMRI study. METHODS: Patients with schizophrenia and healthy controls performed an adaptive version of the Eriksen Flanker task that was specifically designed to ensure a comparable number of errors between groups. RESULTS: We included 27 patients with schizophrenia and 27 healthy controls in our study. The between-groups comparison replicated the classic finding of reduced activation in the midcingulate cortex (MCC) in patients with schizophrenia during the commission of errors while controlling for confounding factors, such as task performance and error frequency, which have been neglected in many previous studies. Subsequent psychophysiological interaction analysis revealed aberrant functional connectivity (FC) between the right AI and regions in the inferior frontal gyrus and temporoparietal junction. Additionally, FC between the MCC and the dorsolateral prefrontal cortex was reduced. LIMITATIONS: As we examined a sample of medicated patients, effects of antipsychotic medication may have influenced our results. CONCLUSION: Overall, it appears that schizophrenia is associated with impairment of networks associated with detection of errors, refocusing of attention, superordinate guiding of cognitive control and their respective coordination.

A single-trial estimation of the feedback-related negativity and its relation to BOLD responses in a time-estimation task.

An event-related potential (ERP) component reliably associated with feedback processing and well studied in humans is the feedback-related negativity (FRN), which is assumed to indicate activation of midcingulate cortex (MCC) neurons. However, recent approaches have conceptualized this frontocentral ERP component as reflecting at least partially a reward positivity associated with activation in reward-related brain regions, in line with fMRI studies investigating feedback processing in the context of reward evaluation. To discover convergence of electrophysiological and BOLD responses elicited by performance feedback, we concurrently recorded EEG and fMRI during a time-estimation task. The ERP showed relatively more negative amplitudes to negative than to positive feedback. Conventional analyses of fMRI data revealed activation of a number of areas, including ventral striatum, anterior cingulate cortex, and medial prefrontal cortex to positive versus negative feedback. Most importantly, when using single-trial amplitudes of electrophysiological feedback signals to estimate hemodynamic responses, we found feedback-related BOLD-responses in ventral striatum, midcingulate, and midfrontal cortices to positive but not to negative feedback associated with feedback signals in the time range of the FRN. Specifically, activation in these areas increased as amplitudes became more positive. These findings suggest that, in the time-estimation task, a positivity elicited by reward is associated with brain activation in several reward-related brain regions and is driving differential ERP responses in the time range of the FRN.

Somatosensory spatial attention modulates amplitudes, latencies, and latency jitter of laser-evoked brain potentials.

Several studies provided evidence that the amplitudes of laser-evoked potentials (LEPs) are modulated by attention. However, previous reports were based on across-trial averaging of LEP responses at the expense of losing information about intertrial variability related to attentional modulation. The aim of this study was to investigate the effects of somatosensory spatial attention on single-trial parameters (i.e., amplitudes, latencies, and latency jitter) of LEP components (N2 and P2). Twelve subjects participated in a sustained spatial attention paradigm while noxious laser stimuli (left hand) and noxious electrical stimuli (right hand) were sequentially delivered to the dorsum of the respective hand with nonnoxious air puffs randomly interspersed within the sequence of noxious stimuli. Participants were instructed to mentally count all stimuli (i.e., noxious and nonnoxious) applied to the attended location. Laser stimuli, presented to the attended hand (ALS), elicited larger single-trial amplitudes of the N2 component compared with unattended laser stimuli (ULS). In contrast, single-trial amplitudes of the P2 component were not significantly affected by spatial attention. Single-trial latencies of the N2 and P2 were significantly smaller for ALS vs. ULS. Additionally, the across-trial latency jitter of the N2 component was reduced for ALS. Conversely, the latency jitter of the P2 component was smaller for ULS compared with ALS. With the use of single-trial analysis, the study provided new insights into brain dynamics of LEPs related to spatial attention. Our results indicate that single-trial parameters of LEP components are differentially modulated by spatial attention.

Brain activation to briefly presented emotional words: effects of stimulus awareness.

It is unknown to what extent briefly presented emotional words can be processed without awareness. By means of two independent functional magnetic resonance imaging studies, using either a block or an event-related design, we investigated brain activation to very briefly presented threat related and neutral words during two backward masking conditions (with and without gap between target and mask). In both experiments, emotional words were perceived during the supraliminal "with gap" condition, but they were not recognized during the subliminal "without gap" condition, as indicated by signal detection theory analysis. Imaging results of both experiments showed increased activation of the amygdala, the medial prefrontal cortex and language-processing cortical areas to negative versus neutral words during supraliminal but not subliminal conditions. These results suggest that even very briefly presented emotional words are capable of triggering increased cortical and subcortical processing; however, only when awareness of these stimuli is given.

Cortical reorganization after macroreplantation at the upper extremity: a magnetoencephalographic study.

With the development of microsurgical techniques, replantation has become a feasible alternative to stump treatment after the amputation of an extremity. It is known that amputation often induces phantom limb pain and cortical reorganization within the corresponding somatosensory areas. However, whether replantation reduces the risk of comparable persisting pain phenomena as well as reorganization of the primary somatosensory cortex is still widely unknown. Therefore, the present study aimed to investigate the potential development of persistent pain and cortical reorganization of the hand and lip areas within the sensory cortex by means of magnetoencephalographic dipole analyses after replantation of a traumatically amputated upper limb proximal to the radiocarpal joint. Cortical reorganization was investigated in 13 patients with limb replantation using air puff stimulation of the phalanges of both thumbs and both corners of the lower lip. Displacement of the centre of gravity of lip and thumb representations and increased cortical activity were found in the limb and face areas of the primary somatosensory cortex contralateral to the replanted arm when compared to the ipsilateral hemisphere. Thus, cortical reorganization in the primary somatosensory cortex also occurs after replantation of the upper extremity. Patients' reports of pain in the replanted body part were negatively correlated with the amount of cortical reorganization, i.e. the more pain the patients reported, the less reorganization of the subjects' hand representation within the primary somatosensory cortex was observed. Longitudinal studies in patients after macroreplantation are necessary to assess whether the observed reorganization in the primary somatosensory cortex is a result of changes within the representation of the replanted arm and/or neighbouring representations and to assess the relationship between the development of persistent pain and reorganization.

Effects of social context on feedback-related activity in the human ventral striatum.

It is now well established that activation of the ventral striatum (VS) encodes feedback related information, in particular, aspects of feedback validity, reward magnitude, and reward probability. More recent findings also point toward a role of VS in encoding social context of feedback processing. Here, we investigated the effect of social observation on neural correlates of feedback processing. To this end, subjects performed a time estimation task and received positive, negative, or uninformative feedback. In one half of the experiment subjects thought that an experimenter closely monitored their face via a camera. We successfully replicated an elevated VS response to positive relative to negative feedback. Further, our data demonstrate that this reward-related activation of the VS is increased during observation by others. Using uninformative feedback as reference condition, we show that specifically VS activation during positive feedback was modulated by observation manipulation. Our findings support accounts which posit a role of VS in integrating social context into the processing of feedback and, in doing so, signaling its social relevance.

Neural correlates of anticipation and processing of performance feedback in social anxiety.

Fear of negative evaluation, such as negative social performance feedback, is the core symptom of social anxiety. The present study investigated the neural correlates of anticipation and perception of social performance feedback in social anxiety. High (HSA) and low (LSA) socially anxious individuals were asked to give a speech on a personally relevant topic and received standardized but appropriate expert performance feedback in a succeeding experimental session in which neural activity was measured during anticipation and presentation of negative and positive performance feedback concerning the speech performance, or a neutral feedback-unrelated control condition. HSA compared to LSA subjects reported greater anxiety during anticipation of negative feedback. Functional magnetic resonance imaging results showed deactivation of medial prefrontal brain areas during anticipation of negative feedback relative to the control and the positive condition, and medial prefrontal and insular hyperactivation during presentation of negative as well as positive feedback in HSA compared to LSA subjects. The results indicate distinct processes underlying feedback processing during anticipation and presentation of feedback in HSA as compared to LSA individuals. In line with the role of the medial prefrontal cortex in self-referential information processing and the insula in interoception, social anxiety seems to be associated with lower self-monitoring during feedback anticipation, and an increased self-focus and interoception during feedback presentation, regardless of feedback valence.

Gray matter changes following limb amputation with high and low intensities of phantom limb pain.

Limb amputation and chronic phantom limb pain (PLP) are both associated with neural alterations at all levels of the neuraxis. We investigated gray matter volume of 21 upper limb amputees and 14 healthy control subjects. Results demonstrate that amputation is associated with reduced gray matter in areas in the motor cortex representing the amputated limb. Additionally, patients show an increase in gray matter in brain regions that belong to the dorsal and ventral visual stream. We subdivided the patient group into patients with medium to high PLP (HPLP; N = 11) and those with slight PLP (SPLP; N = 10). HPLP patients showed reduced gray matter in brain areas involved in pain processing. SPLP patients showed a significant gray matter increase in regions of the visual stream. Results indicate that all patients may have an enhanced need for visual control to compensate the lack of sensory feedback of the missing limb. As we found these alterations primarily in the SPLP patient group, successful compensation may have an impact on PLP development. Therefore, we hypothesize that visual adaptation mechanisms may compensate for the lack of sensorimotor feedback and may therefore function as a protection mechanism against high PLP development.

Neuroscientific results of experimental studies on the control of acute pain with hypnosis and suggested analgesia.

This narrative review summarizes a representative collection of electrophysiological and imaging studies on the neural processes and brain sources underlying hypnotic trance and the effects of hypnotic suggestions on the processing of experimentally induced painful events. It complements several reviews on the effect of hypnosis on brain processes and structures of chronic pain processing. Based on a summary of previous findings on the neuronal processing of experimentally applied pain stimuli and their effects on neuronal brain structures in healthy subjects, three neurophysiological methods are then presented that examine which of these neuronal processes and structures get demonstrably altered by hypnosis and can thus be interpreted as neuronal signatures of the effect of analgesic suggestions: (A) On a more global neuronal level, these are electrical processes of the brain that can be recorded from the cranial surface of the brain with magnetoencephalography (MEG) and electroencephalography (EEG). (B) On a second level, so-called evoked (EPs) or event-related potentials (ERPs) are discussed, which represent a subset of the brain electrical parameters of the EEG. (C) Thirdly, imaging procedures are summarized that focus on brain structures involved in the processing of pain states and belong to the main imaging procedures of magnetic resonance imaging (MRI/fMRI) and positron emission tomography (PET). Finally, these different approaches are summarized in a discussion, and some research and methodological suggestions are made as to how this research could be improved in the future.

Effects of temporary functional deafferentation on the brain, sensation, and behavior of stroke patients.

Following stroke, many patients suffer from chronic motor impairment and reduced somatosensation in the stroke-affected body parts. Recent experimental studies suggest that temporary functional deafferentation (TFD) of parts of the stroke-affected upper limb or of the less-affected contralateral limb might improve the sensorimotor capacity of the stroke-affected hand. The present study sought evidence of cortical reorganization and related sensory and motor improvements following pharmacologically induced TFD of the stroke-affected forearm. Examination was performed during 2 d of Constraint-Induced Movement Therapy. Thirty-six human patients were deafferented on the stroke-affected forearm by an anesthetic cream (containing lidocaine and prilocaine) on one of the 2 d, and a placebo cream was applied on the other. The order of TFD and placebo treatment was counterbalanced across patients. Somatosensory and motor performance were assessed using a Grating orienting task and a Shape-sorter-drum task, and with somatosensory-evoked magnetic fields. Evoked magnetic fields showed significant pre- to postevaluation magnitude increases in response to tactile stimulation of the thumb of the stroke-affected hand during TFD but not following placebo treatment. We also observed a rapid extension of the distance between cortical representations of the stroke-affected thumb and little finger following TFD but not following placebo treatment. Moreover, somatosensory and motor performance of the stroke-affected hand was significantly enhanced during TFD but not during placebo treatment. Thus, pharmacologically induced TFD of a stroke-affected forearm might improve the somatosensory and motor functions of the stroke-affected upper limb, accompanied by cortical plasticity.

Stimulation of peroneal nerves reveals maintained somatosensory representation in transtibial amputees.

Introduction: Several studies have found changes in the organization of the primary somatosensory cortex (SI) after amputation. This SI reorganization was mainly investigated by stimulating neighboring areas to amputation. Unexpectedly, the somatosensory representation of the deafferented limb has rarely been directly tested. Methods: We stimulated the truncated peroneal nerve in 24 unilateral transtibial amputees and 15 healthy controls. The stimulation intensity was adjusted to make the elicited percept comparable between both stimulation sides. Neural sources of the somatosensory-evoked magnetic fields (SEFs) to peroneal stimulation were localized in the contralateral foot/leg areas of SI in 19 patients and 14 healthy controls. Results: We demonstrated the activation of functionally preserved cortical representations of amputated lower limbs. None of the patients reported evoked phantom limb pain (PLP) during stimulation. Stimulation that evoked perceptions in the foot required stronger intensities on the amputated side than on the intact side. In addition to this, stronger stimulation intensities were required for amputees than for healthy controls. Exploratorily, PLP intensity was neither associated with stimulation intensity nor dipole strength nor with differences in Euclidean distances (between SEF sources of the healthy peroneus and mirrored SEF sources of the truncated peroneus). Discussion: Our results provide hope that the truncated nerve may be used to establish both motor control and somatosensory feedback via the nerve trunk when a permanently functional connection between the nerve trunk and the prosthesis becomes available.