Elsevier

NeuroImage

Volume 46, Issue 4, 15 July 2009, Pages 1082-1090
NeuroImage

Modulation of alpha oscillations in insular cortex reflects the threat of painful stimuli

https://doi.org/10.1016/j.neuroimage.2009.03.034Get rights and content

Abstract

Pain is a sensory and emotional experience that involves numerous brain areas. Among these areas the insular cortex has been shown to be involved in the expectation and processing of pain. Alpha power modulation has been associated with the experience of pain. The aim of this study was to test the hypothesis that the threat of a painful stimulus affects alpha rhythm oscillation in the insular cortex and to find the time intervals during which the insular cortex is most active. We used a beamforming method in the frequency domain to estimate alpha power associated with source activity during psychologically different conditions, namely a sequence of nonpainful somatosensory stimuli (non-threatening condition) and a sequence of nonpainful stimuli randomly intermixed with painful stimuli (threatening condition). The results revealed that the anterior insula alone was involved during the threat of painful stimuli. Conversely, the posterior insula – as well as other brain areas such as SII – was involved in the processing of somatosensory stimuli regardless their painfulness. Additionally, the involvement of the anterior insula should not be accounted for by fear, arousal, habituation effect or by the occurrence of randomly interleaved different stimuli, but it is likely to be related mainly to expectancy mechanisms enhancing activity of specific neuronal populations.

Introduction

Painful stimulation activates numerous areas within the brain (Melzack and Wall, 1965). The hypothalamus, the thalamus, the limbic system and several areas in the cortex play a role in processing nociceptive information at various levels (Treede et al., 1999). Several neuroimaging techniques were used to localize pain-related responses in the brain. Functional magnetic resonance imaging (fMRI) studies showed, with good spatial resolution, brain responses to pain (Christmann et al., 2007, Helmchen et al., 2008, Kwan et al., 2000). Electroencephalographic (EEG) and magnetoencephalographic (MEG) results on brain activity after painful stimulation, indicated dipolar activation of the secondary somatosensory cortex (SII) (Chen et al., 2006, Hari et al., 1997), the cingulate region (Bentley et al., 2003, Bromm, 2004), the anterior insular cortex (Bentley et al., 2001, Sami et al., 2006), and of the frontal areas (Brown et al., 2008a, Valeriani et al., 2000). Moreover, using functional neuroimaging, many groups attempted to distinguish brain responses related to the expectation of pain from those associated with the actual experience of pain (Ploghaus et al., 1999, Sawamoto et al., 2000, Koyama et al., 2005). Specifically, Ploghaus et al. found that the expectation of pain activated sites within the insular cortex, the medial frontal lobe and cerebellum, distinct from but close to locations identified during the experience of pain. The combined physiological/fMRI study of Koyama et al. delineated the mechanisms supporting expectation/modulation of pain within the insular areas and the cingulate cortex, associating the duration of the expectation phase to the intensity of perceived pain. Both studies suggested that the insular cortex was associated with the expectation and processing of painful stimuli. In addition, fMRI studies revealed that the insula had an important role in the experience of a number of basic emotions including, anger (Denson et al., 2009), fear (Alvarez et al., 2008), disgust (Mataix-Cols et al., 2008) and in multimodal integration and visceromotor control (Augustine, 1996).

fMRI studies evidenced the role that the insular region plays in the expectation of pain, but they did not provide detailed information on the timing of the insular activation. Electromagnetic techniques may provide the necessary time accuracy to address this issue by means of negative slow fields or potentials and power modulation of brain rhythms. By means of EEG technique, Stimulus-Preceding Negativity was observed when anticipating pain and neural correlates were estimated using tomographic source localization (Brown et al., 2008a). Magnetoencephalographic recordings indicated power changes of cortical oscillations linked to the response to an event (Ploner et al., 2006a, Salmelin et al., 2000). For example, electromagnetic recording evidenced that alpha power modulation was correlated to excitability in the somatosensory system after the presentation of painful stimuli on a single trial basis (Ploner et al., 2006b). Brain rhythm modulation was also evidenced during painful stimuli expectation (Babiloni et al., 2005, Del Percio et al., 2006). However, these studies did not identify specific cortical or subcortical structures involved in pain expectation, and no study examined the contribution of autonomic arousal, anxiety and fear on brain activity changes during the threat of a possible painful stimulus.

The aim of the present study was to test the hypothesis that the threat of a painful stimulus affected alpha rhythm oscillation in the insular cortex and to find the time intervals during which the insular cortex was most active. To properly characterize this area, we modified the Linear Constrained Minimum Variance (LCMV) beamforming method (Van Veen et al., 1997) to operate in the frequency domain (Gross et al., 2001). Insular cortex activity was characterized during the time intervals preceding and following threatening (either painful or nonpainful) and non-threatening (nonpainful) somatosensory stimulation. Heart rate values were used to evaluate if the threat of painful stimuli was accompanied by significant fear, anxiety and/or alteration of affect (Rhudy and Meagher, 2000). As a control, cingulate cortex and SII were studied as well.

Section snippets

Subjects

The experiment was performed on 13 right handed healthy volunteers (7 females) aged 20–31 years (mean, 24 ± 4). None of the subjects suffered from disease that might affect somatosensory and pain perception. Informed consent was obtained from each subject prior to the study. The protocol was approved by the Local Ethics Committee and conformed to the principle of the Helsinki Declaration.

Experimental paradigm

The paradigm used sequences of painful (PS) and nonpainful (NP) somatosensory electrical stimuli. PS consisted

Results

All subjects identified PS-thr as a clear painful stimulus. For a representative subject Fig. 3 shows mean evoked responses recorded from all magnetic channels for the nonpainful stimulation on the dorsum (NPD-c) and for the painful stimulation (PS-thr) induced by the needle electrode. Of note, differently from NPD-c the evoked response following PS-thr doesn't show peaks around 20 and 35 ms. All subjects reported no intensity difference between NPM-thr and NPM-nthr and no difference was

Methodological remarks

We used epidermal electrical stimulation to elicit painful sensation since it was successful used by Inui (Inui et al., 2002) to stimulate Aδ fibres without excitation of the faster Aβ ones (Garcia-Larrea et al., 2003). Although we used a higher current intensity for stimulation than Inui we didn't see any brain activation at 20–50 ms after stimulus, suggesting that no Aβ afferents were stimulated. The subjects rated the delivered painful stimuli as moderate pain (level 2). Moreover differences

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