The lack of clear understanding of the pathophysiology of chronic pain could explain why we currently have only a few effective treatments. Understanding how pain relief is realised during placebo analgesia could help develop improved treatments for chronic pain. Here, we tested whether experimental placebo analgesia was associated with altered resting-state cortical activity in the alpha frequency band of the electroencephalogram (EEG). Alpha oscillations have been shown to be influenced by top-down processes, which are thought to underpin the placebo response.
Seventy-three healthy volunteers, split into placebo or control groups, took part in a well-established experimental placebo procedure involving treatment with a sham analgesic cream. We recorded ongoing (resting) EEG activity before, during, and after the sham treatment.
We show that resting alpha activity is modified by placebo analgesia. Post-treatment, alpha activity increased significantly in the placebo group only (p < 0.001). Source analysis suggested that this alpha activity might have been generated in medial components of the pain network, including dorsal anterior cingulate cortex, medial prefrontal cortex, and left insula.
These changes are consistent with a cognitive state of pain expectancy, a key driver of the placebo analgesic response. The manipulation of alpha activity may therefore present an exciting avenue for the development of treatments that directly alter endogenous processes to better control pain.
The electrically-evoked compound action potential (ECAP) is the synchronous whole auditory nerve activity in response to an electrical stimulus, and can be recorded in situ on cochlear implant (CI) electrodes. A novel procedure (ECAP-ICA) to isolate the ECAP from the stimulation artifact, based on independent component analysis (ICA), is described here. ECAPs with artifact (raw-ECAPs) were sequentially recorded for the same stimulus on 9 different intracochlear recording electrodes. The raw-ECAPs were fed to ICA, which separated them into independent sources. Restricting the ICA projection to 4 independent components did not induce under-fitting and was found to explain most of the raw-data variance. The sources were identified and only the source corresponding to the neural response was retained for artifact-free ECAP reconstruction. The validity of the ECAP-ICA procedure was supported as follows: N1 and P1 peaks occurred at usual latencies; and ECAP-ICA and artifact amplitude-growth functions (AGFs) had different slopes. Concatenation of raw-ECAPs from multiple stimulus currents, including some below the ECAP-ICA threshold, improved the source separation process. The main advantage of ECAP-ICA is that use of maskers or alternating polarity stimulation are not needed.
•Novel technique to cancel artifact in electrically-evoked compound action potentials.•No maskers or alternate polarity are required.•ECAPs output from the procedure are compared to forward-masking technique.
AN, auditory nerve; CI, cochlear implant; CI24RE, Cochlear® Nucleus Freedom™ cochlear implant – 22 active electrodes and 2 ground electrodes; ECAP, electrically-evoked compound action potential; ECAP-FM, ECAP obtained with the forward-masking technique; ECAP-ICA, ECAP obtained with the ICA artifact rejection technique; ICA, independent component analysis; IC, independent component (or source); JADE-R, joint approximate diagonalisation of the cross-cumulants eigenmatrices (computational implementation of ICA); MP1, extracochlear ground electrode; MP2, ground electrode placed on the case of the cochlear implant; N1P1, peak-to-peak voltage difference measurement of ECAP amplitude; RMS, root mean square; SNR, signal to noise ratio
It is well established that mood influences many cognitive processes, such as learning and executive functions. Although statistical learning is assumed to be part of our daily life, as mood does, the influence of mood on statistical learning has never been investigated before. In the present study, a sad vs. neutral mood was induced to the participants through the listening of stories while they were exposed to a stream of visual shapes made up of the repeated presentation of four triplets, namely sequences of three shapes presented in a fixed order. Given that the inter-stimulus interval was held constant within and between triplets, the only cues available for triplet segmentation were the transitional probabilities between shapes. Direct and indirect measures of learning taken either immediately or 20 minutes after the exposure/mood induction phase revealed that participants learned the statistical regularities between shapes. Interestingly, although participants from the sad and neutral groups performed similarly in these tasks, subjective measures (confidence judgments taken after each trial) revealed that participants who experienced the sad mood induction showed increased conscious access to their statistical knowledge. These effects were not modulated by the time delay between the exposure/mood induction and the test phases. These results are discussed within the scope of the robustness principle and the influence of negative affects on processing style.
Placebo analgesia (PA) is accompanied by decreased activity in pain-related brain regions, but also by greater prefrontal cortex (PFC) activation, which has been suggested to reflect increases in top-down cognitive control and regulation of pain. Here we test whether PA is associated with altered prefrontal monitoring functions that could adjust nociceptive processing to a mismatch between expected and experienced pain. We recorded event-related potentials to response errors in a go/nogo task during placebo vs. a matched control condition. Error commission was associated with two well-described components, the error-related negativity (ERN) and the error positivity (Pe). Results show that the Pe, but not the ERN, was amplified during placebo analgesia compared to the control condition, with neural sources in the lateral and medial PFC. This Pe increase was driven by participants showing a placebo-induced change in pain tolerance, but was absent in the group of non-responders. Our results shed new light on the possible functional mechanisms underlying PA, suggesting a placebo-induced transient change in prefrontal error monitoring and control functions.
Mania is characterised by increased impulsivity and risk-taking, and psychological accounts argue that these features may be due to hypersensitivity to reward. The neurobiological mechanisms remain poorly understood. Here we examine reinforcement learning and sensitivity to both reward and punishment outcomes in hypomania-prone individuals not receiving pharmacotherapy.
We recorded EEG from 45 healthy individuals split into three groups by low, intermediate and high self-reported hypomanic traits. Participants played a computerised card game in which they learned the reward contingencies of three cues. Neural responses to monetary gain and loss were measured using the feedback-related negativity (FRN), a component implicated in motivational outcome evaluation and reinforcement learning.
As predicted, rewards elicited a smaller FRN in the hypomania-prone group relative to the low hypomania group, indicative of greater reward responsiveness. The hypomania-prone group also showed smaller FRN to losses, indicating diminished response to negative feedback.
Our findings indicate that proneness to hypomania is associated with both reward hypersensitivity and discounting of punishment. This positive evaluation bias may be driven by aberrant reinforcement learning signals, which fail to update future expectations. This provides a possible neural mechanism explaining risk-taking and impaired reinforcement learning in BD. Further research will be needed to explore the potential value of the FRN as a biological vulnerability marker for mania and pathological risk-taking.
The therapeutic response to a drug treatment is a mixture of direct pharmacological action and placebo effect. Therefore, harnessing the positive aspects of the placebo effect and reducing the negative ones could potentially benefit the patient. This article is aimed at providing an overview for clinicians of the importance of contextual psychosocial variables in determining treatment response, and the specific focus is on determinants of the placebo response. A better understanding of the physiological, psychological, and social mechanisms of placebo may aid in predicting which contexts have the greatest potential for inducing positive treatment responses. We examine the evidence for the role of psychological traits, including optimism, pessimism, and the effect of patient expectations on therapeutic outcome. We discuss the importance of the patient-practitioner relationship and how this can be used to enhance the placebo effect, and we consider the ethical challenges of using placebos in clinical practice.
Learning to fear danger in the environment is essential to survival, but dysregulation of the fear system is at the core of many anxiety disorders. As a consequence, a great interest has emerged in developing strategies for suppressing fear memories in maladaptive cases. Recent research has focused in the process of reconsolidation where memories become labile after being retrieved. In a behavioral manipulation, Schiller et al., (2010) reported that extinction training, administrated during memory reconsolidation, could erase fear responses. The implications of this study are crucial for the possible treatment of anxiety disorders without the administration of drugs. However, attempts to replicate this effect by other groups have been so far unsuccessful. We sought out to reproduce Schiller et al., (2010) findings in a different fear conditioning paradigm based on auditory aversive stimuli instead of electric shock. Following a within-subject design, participants were conditioned to two different sounds and skin conductance response (SCR) was recorded as a measure of fear. Our results demonstrated that only the conditioned stimulus that was reminded 10 minutes before extinction training did not reinstate a fear response after a reminder trial consisting of the presentation of the unconditioned stimuli. For the first time, we replicated Schiller et al., (2010) behavioral manipulation and extended it to an auditory fear conditioning paradigm.
High-pain expectancy increases pain and pain-related brain activity, creating a cycle of psychologically maintained pain. Though these effects are robust, little is known about how expectancy works and what psychological processes either support or mitigate its effects. To address this, we independently manipulated pain expectancy and “top-down” attention to the body, and examined their effects on both a performance-based measure of body-focus and heat-induced pain. Multi-level mediation analyses showed that high-pain expectancy substantially increased pain, replicating previous work. However, attention to the body reduced pain, partially suppressing the effects of expectancy. Furthermore, increased body-focus had larger pain-reducing effects when pain expectancy was high, suggesting that attempts to focus on external distractors are counterproductive in this situation. Overall, the results show that attention to the body cannot explain pain-enhancing expectancy effects, and that focusing on sensory/discriminative aspects of pain might be a useful pain-regulation strategy when severe pain is expected.
Attention can be directed to particular spatial locations, or to objects that appear at anticipated points in time. While most work has focused on spatial or temporal attention in isolation, we investigated covert tracking of smoothly moving objects, which requires continuous coordination of both. We tested two propositions about the neural and cognitive basis of this operation: first that covert tracking is a right hemisphere function, and second that pre-motor components of the oculomotor system are responsible for driving covert spatial attention during tracking. We simultaneously recorded event related potentials (ERPs) and eye position while participants covertly tracked dots that moved leftward or rightward at 12 or 20°/s. ERPs were sensitive to the direction of target motion. Topographic development in the leftward motion was a mirror image of the rightward motion, suggesting that both hemispheres contribute equally to covert tracking. Small shifts in eye position were also lateralized according to the direction of target motion, implying covert activation of the oculomotor system. The data addresses two outstanding questions about the nature of visuospatial tracking. First, covert tracking is reliant upon a symmetrical frontoparietal attentional system, rather than being right lateralized. Second, this same system controls both pursuit eye movements and covert tracking.
Visual scene recognition is a dynamic process through which incoming sensory information is iteratively compared with predictions regarding the most likely identity of the input stimulus. In this study, we used a novel progressive unfolding task to characterize the accumulation of perceptual evidence prior to scene recognition, and its potential modulation by the emotional valence of these scenes. Our results show that emotional (pleasant and unpleasant) scenes led to slower accumulation of evidence compared to neutral scenes. In addition, when controlling for the potential contribution of non-emotional factors (i.e., familiarity and complexity of the pictures), our results confirm a reliable shift in the accumulation of evidence for pleasant relative to neutral and unpleasant scenes, suggesting a valence-specific effect. These findings indicate that proactive iterations between sensory processing and top-down predictions during scene recognition are reliably influenced by the rapidly extracted (positive) emotional valence of the visual stimuli. We interpret these findings in accordance with the notion of a genuine positivity offset during emotional scene recognition.
A number of studies have shown that emotionally arousing stimuli are preferentially processed in the human brain. Whether or not this preference persists under increased perceptual load associated with a task at hand remains an open question. Here we manipulated two possible determinants of the attentional selection process, perceptual load associated with a foreground task and the emotional valence of concurrently presented task-irrelevant distractors. As a direct measure of sustained attentional resource allocation in early visual cortex we used steady-state visual evoked potentials (SSVEPs) elicited by distinct flicker frequencies of task and distractor stimuli. Subjects either performed a detection (low load) or discrimination (high load) task at a centrally presented symbol stream that flickered at 8.6 Hz while task-irrelevant neutral or unpleasant pictures from the International Affective Picture System (IAPS) flickered at a frequency of 12 Hz in the background of the stream. As reflected in target detection rates and SSVEP amplitudes to both task and distractor stimuli, unpleasant relative to neutral background pictures more strongly withdrew processing resources from the foreground task. Importantly, this finding was unaffected by the factor ‘load’ which turned out to be a weak modulator of attentional processing in human visual cortex.
Alcohol use during adolescence has profound and enduring consequences on decision-making under risk. However, the fundamental psychological processes underlying these changes are unknown. Here, we show that alcohol use produces over-fast learning for better-than-expected, but not worse-than-expected, outcomes without altering subjective reward valuation. We constructed a simple reinforcement learning model to simulate altered decision making using behavioral parameters extracted from rats with a history of adolescent alcohol use. Remarkably, the learning imbalance alone was sufficient to simulate the divergence in choice behavior observed between these groups of animals. These findings identify a selective alteration in reinforcement learning following adolescent alcohol use that can account for a robust change in risk-based decision making persisting into later life.
Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.
Symptoms of Major Depressive Disorder (MDD) are hypothesized to arise from dysfunction in brain networks linking the limbic system and cortical regions. Alterations in brain functional cortical connectivity in resting-state networks have been detected with functional imaging techniques, but neurophysiologic connectivity measures have not been systematically examined. We used weighted network analysis to examine resting state functional connectivity as measured by quantitative electroencephalographic (qEEG) coherence in 121 unmedicated subjects with MDD and 37 healthy controls. Subjects with MDD had significantly higher overall coherence as compared to controls in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–20 Hz) frequency bands. The frontopolar region contained the greatest number of “hub nodes” (surface recording locations) with high connectivity. MDD subjects expressed higher theta and alpha coherence primarily in longer distance connections between frontopolar and temporal or parietooccipital regions, and higher beta coherence primarily in connections within and between electrodes overlying the dorsolateral prefrontal cortical (DLPFC) or temporal regions. Nearest centroid analysis indicated that MDD subjects were best characterized by six alpha band connections primarily involving the prefrontal region. The present findings indicate a loss of selectivity in resting functional connectivity in MDD. The overall greater coherence observed in depressed subjects establishes a new context for the interpretation of previous studies showing differences in frontal alpha power and synchrony between subjects with MDD and normal controls. These results can inform the development of qEEG state and trait biomarkers for MDD.
Using magnetoencephalography (MEG), we investigated the influence of long term musical training on the processing of partly imagined tone patterns (imagery condition) compared to the same perceived patterns (perceptual condition). The magnetic counterpart of the mismatch negativity (MMNm) was recorded and compared between musicians and non-musicians in order to assess the effect of musical training on the detection of deviants to tone patterns. The results indicated a clear MMNm in the perceptual condition as well as in a simple pitch oddball (control) condition in both groups. However, there was no significant mismatch response in either group in the imagery condition despite above chance behavioral performance in the task of detecting deviant tones. The latency and the laterality of the MMNm in the perceptual condition differed significantly between groups, with an earlier MMNm in musicians, especially in the left hemisphere. In contrast the MMNm amplitudes did not differ significantly between groups. The behavioral results revealed a clear effect of long-term musical training in both experimental conditions. The obtained results represent new evidence that the processing of tone patterns is faster and more strongly lateralized in musically trained subjects, which is consistent with other findings in different paradigms of enhanced auditory neural system functioning due to long-term musical training.
With this study we wanted to test the hypothesis that individual like and dislike as occurring in relation to brand attitude can be objectively assessed. First, individuals rated common brands with respect to subjective preference. Then, they volunteered in an experiment during which their most liked and disliked brand names were visually presented while three different objective measures were taken. Participant's eye blinks as responses to acoustic startle probes were registered with electromyography (EMG) (i) and their skin conductance (ii) and their heart rate (iii) were recorded. We found significantly reduced eye blink amplitudes related to liked brand names compared to disliked brand names. This finding suggests that visual perception of liked brand names elicits higher degrees of pleasantness, more positive emotion and approach-oriented motivation than visual perception of disliked brand names. Also, skin conductance and heart rate were both reduced in case of liked versus disliked brand names. We conclude that all our physiological measures highlight emotion-related differences depending on the like and dislike toward individual brands. We suggest that objective measures should be used more frequently to quantify emotion-related aspects of brand attitude. In particular, there might be potential interest to introduce startle reflex modulation to measure emotion-related impact during product development, product design and various further fields relevant to marketing. Our findings are discussed in relation to the idea that self reported measures are most often cognitively polluted.
Impulsivity is the tendency to act without forethought. It is a personality trait commonly used in the diagnosis of many psychiatric diseases. In clinical practice, impulsivity is estimated using written questionnaires. However, answers to questions might be subject to personal biases and misinterpretations. In order to alleviate this problem, eye movements could be used to study differences in decision processes related to impulsivity. Therefore, we investigated correlations between impulsivity scores obtained with a questionnaire in healthy subjects and characteristics of their anticipatory eye movements in a simple smooth pursuit task. Healthy subjects were asked to answer the UPPS questionnaire (Urgency Premeditation Perseverance and Sensation seeking Impulsive Behavior scale), which distinguishes four independent dimensions of impulsivity: Urgency, lack of Premeditation, lack of Perseverance, and Sensation seeking. The same subjects took part in an oculomotor task that consisted of pursuing a target that moved in a predictable direction. This task reliably evoked anticipatory saccades and smooth eye movements. We found that eye movement characteristics such as latency and velocity were significantly correlated with UPPS scores. The specific correlations between distinct UPPS factors and oculomotor anticipation parameters support the validity of the UPPS construct and corroborate neurobiological explanations for impulsivity. We suggest that the oculomotor approach of impulsivity put forth in the present study could help bridge the gap between psychiatry and physiology.
In visual processing, there are marked cultural differences in the tendency to adopt either a global or local processing style. A remote culture (the Himba) has recently been reported to have a greater local bias in visual processing than Westerners. Here we give the first evidence that a greater, and remarkable, attentional selectivity provides the basis for this local bias.
In Experiment 1, Eriksen-type flanker interference was measured in the Himba and in Western controls. In both groups, responses to the direction of a task-relevant target arrow were affected by the compatibility of task-irrelevant distractor arrows. However, the Himba showed a marked reduction in overall flanker interference compared to Westerners. The smaller interference effect in the Himba occurred despite their overall slower performance than Westerners, and was evident even at a low level of perceptual load of the displays. In Experiment 2, the attentional selectivity of the Himba was further demonstrated by showing that their attention was not even captured by a moving singleton distractor.
We argue that the reduced distractibility in the Himba is clearly consistent with their tendency to prioritize the analysis of local details in visual processing.
Schizophrenia is currently diagnosed on the basis of patient reports and clinical observations. A diagnosis based on aetiology is inherently more reliable due to being closer to the disease process than the overt clinical manifestations. Accordingly, recent research in schizophrenia has focused on the development of biomarkers in a bit to improve the reliability and neurobiological relevance of the diagnosis. Visual information processing is one of these promising fields of recent biomarker research.
This article provides an overview of the available literature regarding deficits in schizophrenia detectable through psychophysical (contrast and motion sensitivity, visual backward-masking), ERP (P1 and N1 visual evoked potentials) and oscillatory (signal power and phase-locking factor of evoked oscilations) measures and their validity as trait or state biomarkers of the disease. The methodology included a search on articles related to visual information processing in schizophrenia on the PubMed database.
Biomarker research in schizophrenia is a rapidly expanding area. Evidence exists to suggest that both psychotic and manic symptoms are associated with visual processing abnormalities. A specific impairment confined to the magnocellular component of the visual system might be a trait biomarker of schizophrenia.
schizophrenia; diagnosis; early detection; trait biomarkers; state biomarkers; P1; oscillations; magnocellular pathway
Representations in the cortex are often distributed with graded firing rates in the neuronal populations. The firing rate probability distribution of each neuron to a set of stimuli is often exponential or gamma. In processes in the brain, such as decision-making, that are influenced by the noise produced by the close to random spike timings of each neuron for a given mean rate, the noise with this graded type of representation may be larger than with the binary firing rate distribution that is usually investigated. In integrate-and-fire simulations of an attractor decision-making network, we show that the noise is indeed greater for a given sparseness of the representation for graded, exponential, than for binary firing rate distributions. The greater noise was measured by faster escaping times from the spontaneous firing rate state when the decision cues are applied, and this corresponds to faster decision or reaction times. The greater noise was also evident as less stability of the spontaneous firing state before the decision cues are applied. The implication is that spiking-related noise will continue to be a factor that influences processes such as decision-making, signal detection, short-term memory, and memory recall even with the quite large networks found in the cerebral cortex. In these networks there are several thousand recurrent collateral synapses onto each neuron. The greater noise with graded firing rate distributions has the advantage that it can increase the speed of operation of cortical circuitry.
The neural mechanisms whereby placebo conditioning leads to placebo analgesia remain unclear. In this study we aimed to identify the brain structures activated during placebo conditioning and subsequent placebo analgesia. We induced placebo analgesia by associating a sham treatment with pain reduction and used fMRI to measure brain activity associated with three stages of the placebo response: before, during and after the sham treatment, while participants anticipated and experienced brief laser pain. In the control session participants were explicitly told that the treatment was inactive. The sham treatment group reported a significant reduction in pain rating (p = 0.012). Anticipatory brain activity was modulated during placebo conditioning in a fronto-cingulate network involving the left dorsolateral prefrontal cortex (DLPFC), medial frontal cortex and the anterior mid-cingulate cortex (aMCC). Identical areas were modulated during anticipation in the placebo analgesia phase with the addition of the orbitofrontal cortex (OFC). However, during altered pain experience only aMCC, post-central gyrus and posterior cingulate demonstrated altered activity. The common frontal cortical areas modulated during anticipation in both the placebo conditioning and placebo analgesia phases have previously been implicated in placebo analgesia. Our results suggest that the main effect of placebo arises from the reduction of anticipation of pain during placebo conditioning that is subsequently maintained during placebo analgesia.
Placebo analgesia; Placebo; fMRI; Laser; Conditioning