An analytical method to separate modality-specific and nonspecific sensory components of event-related potentials.

Several models have been developed to analyse cortical activity in response to salient events constituted by multiple sensory modalities. In particular, additive models compare event-related potentials (ERPs) in response to stimuli from two or more concomitant sensory modalities with the ERPs evoked by unimodal stimuli, in order to study sensory interactions. In this approach, components that are not specific to a sensory modality are commonly disregarded, although they likely carry information about stimulus expectation and evaluation, attentional orientation and other cognitive processes. In this study, we present an analytical method to assess the contribution of modality-specific and nonspecific components to the ERP. We developed an experimental setup that recorded ERPs in response to four stimulus types (visual, auditory, and two somatosensory modalities to test for stimulus specificity) in three different conditions (unimodal, bimodal and trimodal stimulation) and recorded the saliency of these stimuli relative to the sensory background. Stimuli were delivered in pairs, in order to study the effects of habituation. To this end, spatiotemporal features (peak amplitudes and latencies at different scalp locations) were analysed using linear mixed models. Results showed that saliency relative to the sensory background increased with the number of concomitant stimuli. We also observed that the spatiotemporal features of modality-specific components derived from this method likely reflect the amount and type of sensory input. Furthermore, the nonspecific component reflected habituation occurring for the second stimulus in the pair. In conclusion, this method provides an alternative to study neural mechanisms of responses to multisensory stimulation.

Opioid Specific Effects on Central Processing of Sensation and Pain: A Randomized, Cross-Over, Placebo-Controlled Study.

Moderate to severe pain is often treated with opioids, but central mechanisms underlying opioid analgesia are poorly understood. Findings thus far have been contradictory and none could infer opioid specific effects. This placebo-controlled, randomized, 2-way cross-over, double-blinded study aimed to explore opioid specific effects on central processing of external stimuli. Twenty healthy male volunteers were included and 3 sets of assessments were done at each of the 2 visits: 1) baseline, 2) during continuous morphine or placebo intravenous infusion and 3) during simultaneous morphine + naloxone or placebo infusion. Opioid antagonist naloxone was introduced in order to investigate opioid specific effects by observing which morphine effects are reversed by this intervention. Quantitative sensory testing, spinal nociceptive withdrawal reflexes (NWR), spinal electroencephalography (EEG), cortical EEG responses to external stimuli and resting EEG were measured and analyzed. Longer lasting pain (cold-pressor test - hand in 2° water for 2 minutes, tetanic electrical), deeper structure pain (bone pressure) and strong nociceptive (NWR) stimulations were the most sensitive quantitative sensory testing measures of opioid analgesia. In line with this, the principal opioid specific central changes were seen in NWRs, EEG responses to NWRs and cold-pressor EEG. The magnitude of NWRs together with amplitudes and insular source strengths of the corresponding EEG responses were attenuated. The decreases in EEG activity were correlated to subjective unpleasantness scores. Brain activity underlying slow cold-pressor EEG (1-4Hz) was decreased, whereas the brain activity underlying faster EEG (8-12Hz) was increased. These changes were strongly correlated to subjective pain relief. This study points to evidence of opioid specific effects on perception of external stimuli and the underlying central responses. The analgesic response to opioids is likely a synergy of opioids acting at both spinal and supra-spinal levels of the central nervous system. Due to the strong correlations with pain relief, the changes in EEG signals during cold-pressor test have the potential to serve as biomarkers of opioid analgesia. PERSPECTIVE: This exploratory study presents evidence of opioid specific effects on the pain system at peripheral and central levels. The findings give insights into which measures are the most sensitive for assessing opioid-specific effects.

Conditioned pain modulation affects the withdrawal reflex pattern to nociceptive stimulation in humans.

Human studies have repeatedly shown that conditioning pain modulation (CPM) exerts an overall descending inhibitory effect over spinal nociceptive activity. Previous studies have reported a reduction of the nociceptive withdrawal reflex (NWR) under CPM. Still, how descending control influences the muscle activation patterns involved in this protective behavior remains unknown. This study aimed to characterize the effects of CPM on the withdrawal pattern assessed by a muscle synergy analysis of several muscles involved in the lower limb NWR. To trigger descending inhibition, CPM paradigm was applied using the cold-pressor test (CPT) as conditioning stimulus. Sixteen healthy volunteers participated. The NWR was evoked by electrical stimulation on the arch of the foot before, during and after the CPT. Electromyographic (EMG) activity of two proximal (rectus femoris and biceps femoris) and two distal (tibialis anterior and soleus) muscles was recorded. A muscle synergy analysis was performed on the decomposition of the EMG signals, based on a non-negative matrix factorization algorithm. Results showed that two synergies (Module I and II) were sufficient to describe the NWR pattern. Under CPM, Module I activation amplitude was significantly reduced in a narrow time-window interval (118-156 ms) mainly affecting distal muscles, whereas Module II activation amplitude was significantly reduced in a wider time-window interval (150-250 ms), predominantly affecting proximal muscles. These findings suggest that proximal muscles are largely under supraspinal control. The descending inhibitory drive exerted onto the spinal cord may adjust the withdrawal pattern by differential recruitment of the muscles involved in the protective behavior.