Elia Valentini

Cognitive aspects of nociception and pain: bridging neurophysiology with cognitive psychology

The event-related brain potentials (ERPs) elicited by nociceptive stimuli are largely influenced by vigilance, emotion, alertness, and attention. Studies that specifically investigated the effects of cognition on nociceptive ERPs support the idea that most of these ERP components can be regarded as the neurophysiological indexes of the processes underlying detection and orientation of attention toward the eliciting stimulus. Such detection is determined both by the salience of the stimulus that makes it pop out from the environmental context (bottom-up capture of attention) and by its relevance according to the subjects goals and motivation (top-down attentional control). The fact that nociceptive ERPs are largely influenced by information from other sensory modalities such as vision and proprioception, as well as from motor preparation, suggests that these ERPs reflect a cortical system involved in the detection of potentially meaningful stimuli for the body, with the purpose to respond adequately to potential threats. In such a theoretical framework, pain is seen as an epiphenomenon of warning processes, encoded in multimodal and multiframe representations of the body, well suited to guide defensive actions. The findings here reviewed highlight that the ERPs elicited by selective activation of nociceptors may reflect an attentional gain apt to bridge a coherent perception of salient sensory events with action selection processes.

Dishabituation of laser-evoked eeg responses: Dissecting the effect of certain and uncertain changes in stimulus modality

The repetition of nociceptive stimuli of identical modality, intensity, and location at short and constant interstimulus intervals (ISIs) determines a strong habituation of the corresponding EEG responses, without affecting the subjective perception of pain. To understand what determines this response habituation, we (i) examined the effect of introducing a change in the modality of the repeated stimulus, and (ii) dissected the relative contribution of bottom–up, stimulus-driven changes in modality and top–down, cognitive expectations of such a change, on both laser-evoked and auditory-evoked EEG responses. Multichannel EEG was recorded while participants received trains of three stimuli (S1–S2–S3, a triplet) delivered to the hand dorsum at 1-sec ISI. S3 belonged either to the same modality as S1 and S2 or to the other modality. In addition, participants were either explicitly informed or not informed of the modality of S3. We found that introducing a change in stimulus modality produced a significant dishabituation of the laser-evoked N1, N2, and P2 waves; the auditory N1 and P2 waves; and the laser- and auditory-induced event-related synchronization and desynchronization. In contrast, the lack of explicit knowledge of a possible change in the sensory modality of the stimulus (i.e., uncertainty) only increased the ascending portion of the laser-evoked and auditory-evoked P2 wave. Altogether, these results indicate that bottom–up novelty resulting from the change of stimulus modality, and not top–down cognitive expectations, plays a major role in determining the habituation of these brain responses.

Systematic review and meta-analysis of psychomotor effects of mobile phone electromagnetic fields

Objectives Over the past 10 years there has been increasing concern about the possible behavioural effects of mobile phone use. This systematic review and meta-analysis focuses on studies published since 1999 on the human cognitive and performance effects of mobile phone-related electromagnetic fields (EMF). Methods PubMed, Biomed, Medline, Biological Sciences, PsychInfo, PsycARTICLES, Environmental Sciences and Pollution Management, Neurosciences Abstracts and Web of Science professional databases were searched and 24 studies selected for meta-analysis. Each study had to have at least one psychomotor measurement result as a main outcome. Data were analysed using standardised mean difference (SMD) as the effect size measure. Results Only three tasks (2-back, 3-back and simple reaction time (SRT)) displayed significant heterogeneity, but after studies with extreme SMD were excluded using sensitivity analysis, the statistical significance disappeared (χ2(7)=1.63, p=0.20; χ2(6)=1.00, p=0.32; χ2(10)=14.04, p=0.17, respectively). Following sensitivity analysis, the effect of sponsorship and publication bias were assessed. Meta-regression indicated a significant effect (b1/40.12, p<0.05) only for the 2-back task with mixed funding (industry and public/charity). Funnel plot inspection revealed a significant publication bias only for two cognitive tasks: SRT (Beggs rank correlation r=0.443; Eggers test b=−0.652) and the subtraction task (Eggers test b=−0.687). Conclusions Mobile phone-like EMF do not seem to induce cognitive and psychomotor effects. Nonetheless, the existence of sponsorship and publication biases should encourage WHO intervention to develop official research standards and guidelines. In addition, future research should address critical and neglected issues such as investigation of repeated, intensive and chronic exposures, especially in highly sensitive populations such as children.

Psychomotor performance is not influenced by brief repeated exposures to mobile phones

The present study investigated the presence of a cumulative effect of brief and repeated exposures to a GSM mobile phone (902.40 MHz, 217 Hz modulated; peak power of 2 W; average power of 0.25 W; SAR = 0.5 W/kg) on psychomotor functions. To this end, after each of 3 15-min exposures, both an acoustic simple reaction time task (SRTT) and a sequential finger tapping task (SFTT) were administered to 24 subjects. The present study was unable to detect the cumulative effects of brief and repeated EMF exposure on human psychomotor performance, although there was a non-statistical trend to shorter reaction times. In summary, these data show an absence of effects with these particular exposure conditions; however, possible cognitive effects induced by different signal characteristics cannot be excluded.

Functional features of nociceptive-induced suppression of alpha band electroencephalographic oscillations

UNLABELLED Nociceptive stimuli can induce a transient suppression of electroencephalographic oscillations in the alpha frequency band (ie, alpha event-related desynchronization, α-ERD). Here we investigated whether α-ERD could be functionally distinguished in 2 temporally and spatially segregated subcomponents as suggested by previous studies. In addition, we tested whether the degree of dependence of nociceptive-induced α-ERD magnitude on the prestimulus α-power would have been larger than the degree of dependence on the poststimulus α-power. Our findings confirmed the dissociation between a sensory-related α-ERD maximally distributed over contralateral central electrodes, and a task-related α-ERD (possibly affected by motor-related activity), maximally distributed at posterior parietal and occipital electrodes. The cortical sources of these activities were estimated to be located at the level of sensorimotor and bilateral occipital cortices, respectively. Importantly, the time course of the α-ERD revealed that functional segregation emerged only at late latencies (400 to 750 ms) whereas topographic similarity was observed at earlier latencies (250 to 350 ms). Furthermore, the nociceptive-induced α-ERD magnitude was significantly more dependent on prestimulus than poststimulus α-power. Altogether these findings provide direct evidence that the nociceptive-induced α-ERD reflects the summation of sensory-related and task-related cortical processes, and that prestimulus fluctuations can remarkably influence the non-phase-locked nociceptive α-ERD. PERSPECTIVE Present results extend the functional understanding of α-oscillation suppression during pain perception and demonstrate the influence of prestimulus variability on this cortical phenomenon. This work has the potential to guide pain clinicians in a more accurate interpretation on physiological and psychological modulations of α-oscillations.

Hypnotic modulation of pain perception and of brain activity triggered by nociceptive laser stimuli.

INTRODUCTION Neuroimaging studies indicate that hypnotic suggestions of increased and decreased pain intensity and unpleasantness may modulate somatosensory and cingulate cortex activity, respectively. METHODS Using a within subject design and a strict subject selection procedure, we tested in High (Highs) and Low (Lows) hypnotically suggestible individuals whether hypnotic suggestions of sensory and affective hypoalgesia or hyperalgesia differentially affected subjective ratings of laser-induced pain and nociceptive-related brain activity in the time- and time-frequency domain. RESULTS Hypnotic modulation of pain intensity and unpleasantness affected subjective ratings of laser-induced pain only in Highs. Such modulation was more specific for unpleasantness manipulation and more evident for suggestions of hyperalgesia. Importantly, Highs and Lows showed increase and decrease of P2a and P2b wave amplitudes and gamma band power, respectively. CONCLUSIONS Hypnotic suggestions exerted a top-down modulatory effect on both evoked and induced-cortical brain responses triggered by selective nociceptive laser inputs. Furthermore, correlation analyses indicated that gamma power modulation and suggestions of hyperalgesia may reflect the process of allocating control resources to salient and threatening sensory-affective dimensions of pain.

The primary somatosensory cortex contributes to the latest part of the cortical response elicited by nociceptive somatosensory stimuli in humans

Nociceptive laser pulses elicit temporally-distinct cortical responses (the N1, N2 and P2 waves of laser-evoked potentials, LEPs) mainly reflecting the activity of the primary somatosensory cortex (S1) contralateral to the stimulated side, and of the bilateral operculoinsular and cingulate cortices. Here, by performing two different EEG experiments and applying a range of analysis approaches (microstate analysis, scalp topography, single-trial estimation), we describe a distinct component in the last part of the human LEP response (P4 wave). We obtained three main results. First, the LEP is reliably decomposed in four main and distinct functional microstates, corresponding to the N1, N2, P2, and P4 waves, regardless of stimulus territory. Second, the scalp and source configurations of the P4 wave follow a clear somatotopical organization, indicating that this response is likely to be partly generated in contralateral S1. Third, single-trial latencies and amplitudes of the P4 are tightly coupled with those of the N1, and are similarly sensitive to experimental manipulations (e.g., to crossing the hands over the body midline), suggesting that the P4 and N1 may have common neural sources. These results indicate that the P4 wave is a clear and distinct LEP component, which should be considered in LEP studies to achieve a comprehensive understanding of the brain response to nociceptive stimulation.

Seeing touch and pain in a stranger modulates the cortical responses elicited by somatosensory but not auditory stimulation

Viewing others pain inhibits the excitability of the motor cortex and also modulates the neural activity elicited by a concomitantly delivered nociceptive somatosensory stimulus. As the neural activity elicited by a transient nociceptive stimulus largely reflects non nociceptive‐specific, multimodal neural processes, here we tested, for the first time, whether the observation of others pain preferentially affects the brain responses elicited by nociceptive stimulation, or instead similarly modulates those elicited by stimuli belonging to a different sensory modality. Using 58‐channel electroencephalography (EEG), we recorded the cortical responses elicited by laser and auditory stimulation during the observation of videoclips showing either noxious or non‐noxious stimulation of a strangers hand. We found that the observation of others pain modulated the cortical activity consisting in an event‐related desynchronization in the β band (β ERD), and elicited by nociceptive laser stimuli, but not by auditory stimuli. Using three different source analysis approaches, we provide converging evidence that such modulation affected neural activity in the contralateral primary sensorimotor cortex. The magnitude of this modulation correlated well with a subjective measure of similarity between the models hand and the onlookers representation of the hand. Altogether, these findings demonstrate that the observation of others pain modulates, in a somatosensory‐specific fashion, the cortical responses elicited by nociceptive stimuli in the sensorimotor cortex contralateral to the stimulated hand. Hum Brain Mapp, 2012.

Intracortical modulation, and not spinal inhibition, mediates placebo analgesia.

Suppression of spinal responses to noxious stimulation has been detected using spinal fMRI during placebo analgesia, which is therefore increasingly considered a phenomenon caused by descending inhibition of spinal activity. However, spinal fMRI is technically challenging and prone to false‐positive results. Here we recorded laser‐evoked potentials (LEPs) during placebo analgesia in humans. LEPs allow neural activity to be measured directly and with high enough temporal resolution to capture the sequence of cortical areas activated by nociceptive stimuli. If placebo analgesia is mediated by inhibition at spinal level, this would result in a general suppression of LEPs rather than in a selective reduction of their late components. LEPs and subjective pain ratings were obtained in two groups of healthy volunteers – one was conditioned for placebo analgesia while the other served as unconditioned control. Laser stimuli at three suprathreshold energies were delivered to the right hand dorsum. Placebo analgesia was associated with a significant reduction of the amplitude of the late P2 component. In contrast, the early N1 component, reflecting the arrival of the nociceptive input to the primary somatosensory cortex (SI), was only affected by stimulus energy. This selective suppression of late LEPs indicates that placebo analgesia is mediated by direct intracortical modulation rather than inhibition of the nociceptive input at spinal level. The observed cortical modulation occurs after the responses elicited by the nociceptive stimulus in the SI, suggesting that higher order sensory processes are modulated during placebo analgesia.

Mismatch responses evoked by nociceptive stimuli

We studied whether nociceptive mismatch negativity (nMMN) could be obtained as result of nociceptive fibers stimulation. The purported nMMN revealed a topography similar to the somatosensory MMN (sMMN), which was observed at the bilateral temporal regions of the scalp. Importantly, only early negativities (100-250 ms) located at these regions revealed a selective modulation associated to the processing of deviancy regardless of the attentional focus. The amplitude modulation of the sMMN had an earlier onset than the nMMN (110 ms vs. 182 ms) as well as a larger difference of latency between the contralateral and the ipsilateral onset of the activity (52 ms vs. 4 ms). Altogether, these observations provide evidence that (a) a nMMN can be elicited by nociceptive stimuli, and (b) the nMMN is topographically similar to the sMMN while differing in latency and possibly in functional organization of their generators.