Filtering the reality: Functional dissociation of lateral and medial pain systems during sleep in humans
TL;DR: While the lateral operculo‐insular system subserving sensory analysis of somatic stimuli remained active during paradoxical‐REM sleep, mid‐anterior cingulate processes related to orienting and avoidance behavior were suppressed, explaining why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject.
Abstract: Behavioral reactions to sensory stimuli during sleep are scarce despite preservation of sizeable cortical responses. To further understand such dissociation, we recorded intracortical field potentials to painful laser pulses in humans during waking and all-night sleep. Recordings were obtained from the three cortical structures receiving 95% of the spinothalamic cortical input in primates, namely the parietal operculum, posterior insula, and mid-anterior cingulate cortex. The dynamics of responses during sleep differed among cortical sites. In sleep Stage 2, evoked potential amplitudes were similarly attenuated relative to waking in all three cortical regions. During paradoxical, or rapid eye movements (REM), sleep, opercular and insular potentials remained stable in comparison with Stage 2, whereas the responses from mid-anterior cingulate abated drastically, and decreasing below background noise in half of the subjects. Thus, while the lateral operculo-insular system subserving sensory analysis of somatic stimuli remained active during paradoxical-REM sleep, mid-anterior cingulate processes related to orienting and avoidance behavior were suppressed. Dissociation between sensory and orienting-motor networks might explain why nociceptive stimuli can be either neglected or incorporated into dreams without awakening the subject.
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TL;DR: The pain matrix is conceptualised here as a fluid system composed of several interacting networks, including posterior parietal, prefrontal and anterior insular areas, which ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits.
Abstract: The pain matrix is conceptualised here as a fluid system composed of several interacting networks. A nociceptive matrix receiving spinothalamic projections (mainly posterior operculoinsular areas) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits. Transition from cortical nociception to conscious pain relies on a second-order network, including posterior parietal, prefrontal and anterior insular areas. Second-order regions are not nociceptive-specific; focal stimulation does not evoke pain, and focal destruction does not produce analgesia, but their joint activation is necessary for conscious perception, attentional modulation and control of vegetative reactions. The ensuing pain experience can still be modified as a function of beliefs, emotions and expectations through activity of third-order areas, including the orbitofrontal and perigenual/limbic networks. The pain we remember results from continuous interaction of these subsystems, and substantial changes in the pain experience can be achieved by acting on each of them. Neuropathic pain (NP) is associated with changes in each of these levels of integration. The most robust abnormality in NP is a functional depression of thalamic activity, reversible with therapeutic manoeuvres and associated with rhythmic neural bursting. Neuropathic allodynia has been associated with enhancement of ipsilateral over contralateral insular activation and lack of reactivity in orbitofrontal/perigenual areas. Although lack of response of perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic pathways due to depression of their contralateral counterpart. This in turn may bias perceptual networks and contribute to the subjective painful experience.
370 citations
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...—Claude Bernard...
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TL;DR: It is contended that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino‐amygdalar pathways can generate implicit memory traces and stimulus‐response abnormal sequences, possibly contributing to long‐standing anxiety or hyperalgesic syndromes in patients surviving coma.
Abstract: The aversive experience we call "pain" results from the coordinated activation of multiple brain areas, commonly described as a "pain matrix". This is not a fixed arrangement of structures but rather a fluid system composed of several interacting networks: A 'nociceptive matrix' includes regions receiving input from ascending nociceptive systems, and ensures the bodily characteristics of physical pain. A further set of structures receiving secondary input supports the 'salience' attributes of noxious stimuli, triggers top-down cognitive controls, and -most importantly- ensures the passage from pre-conscious nociception to conscious pain. Expectations and beliefs can still modulate the conscious experience via activity in supramodal regions with widespread cortical projections such as the ventral tegmental area. Intracortical EEG responses in humans show that nociceptive cortical processing is initiated in parallel in sensory, motor and limbic areas; it progresses rapidly to the recruitment of anterior insular and fronto-parietal networks, and finally to the activation of perigenual, posterior cingulate and hippocampal structures. Functional connectivity between sensory and high-level networks increases during the first second post-stimulus, which may be determinant for access to consciousness. A model is described, progressing from unconscious sensori-motor and limbic processing of spinothalamic and spino-parabrachial input, to an immediate sense of awareness supported by coordinated activity in sensorimotor and fronto-parieto-insular networks, and leading to full declarative consciousness through integration with autobiographical memories and self-awareness, involving posterior cingulate and medial temporal areas. This complete sequence is only present during full vigilance states. We contend, however, that even in unconscious subjects, repeated limbic and vegetative activation by painful stimuli via spino-amygdalar pathways can generate implicit memory traces and stimulus-response abnormal sequences, possibly contributing to long-standing anxiety or hyperalgesic syndromes in patients surviving coma.
82 citations
TL;DR: The results suggest that the human cortex does not shift from sleep to wake in an abrupt binary way, and stereotyped arousals at the thalamic level seem to be associated with different patterns of cortical arousals due to various regulation factors.
65 citations
Cites background from "Filtering the reality: Functional d..."
...Laser stimulation protocol is detailed in Bastuji et al. (2012)....
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...…impossible to explore with scalp EEG, intra-cerebral recordings performed in epileptic patients have proved to be useful in many electrophysiological sleep studies (Nobili et al., 2011; Sarasso et al., 2014; Bastuji et al., 2012; Magnin et al., 2004; Nir et al., 2011; Peter-Derex et al., 2012)....
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TL;DR: Examining the multidimensional construct of pain in concussion/mTBI through a sex lens garners new directions for future longitudinal research on the pain mechanisms involved in postconcussion syndrome.
35 citations
TL;DR: This patient exhibited finger lifts in response to stimulations delivered during paradoxical (REM) sleep, suggesting that during PS, not only the processing of sensory inputs but also the capacity for the sleeper to intentionally indicate his perception could be preserved under particular circumstances is suggested.
Abstract: Sleep disruption by painful stimuli is frequently observed both in clinical and experimental conditions. Nociceptive stimuli produce significantly more arousals (30% of stimuli) than non-nociceptive ones. However, even if they do not interrupt sleep, they can trigger a variety of other reactions. Reflex behaviours in response to nociceptive stimuli can be observed during all sleep stages, and are more likely to occur in association with an arousal than alone. Cardiac activation represents a robust sympathetically driven effect preserved whatever the state of vigilance, even if its magnitude can be modulated by a concomitant cortical arousal. Not withstanding these reactions, incorporation of nociceptive stimuli into dream content remains limited. At cortical level, laser-evoked potential studies demonstrate that the processing of nociceptive stimulations is partly conserved during all sleep stages. Furthermore, when nociceptive stimulations interrupt sleep, the cortical response presents a late component suggesting that the stimulation has to be cognitively processed in order to produce a subsequent arousal. More complex reactions to nociceptive stimulations were occasionally reported. In this context, an epileptic patient with intracerebral electrodes implanted for therapeutic purposes allowed us extending these observations. This patient exhibited finger lifts in response to stimulations delivered during paradoxical (REM) sleep. This motor reaction was previously used during wakefulness to indicate that the stimulation had been perceived. When these finger lifts occurred a systematic re-activation of the anterior cingulate preceded each movement. This observation suggests that during PS, not only the processing of sensory inputs but also the capacity for the sleeper to intentionally indicate his perception could be preserved under particular circumstances.
22 citations
References
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TL;DR: The modifications induced by increasing thermal energy on evoked potentials recorded with electrodes implanted within SII and posterior insula in patients referred for presurgical evaluation of epilepsy are analyzed to assume that insular cortex could be more involved in the triggering of affective recognition of, and motor reaction to, noxious stimuli, whereas SII would be more dedicated to finer-grain discrimination of stimulus intensity.
Abstract: The SII area and the posterior insular region are both activated by thermal stimuli in functional imaging studies. However, controversy remains as to a possible differential encoding of thermal intensity by each of these 2 contiguous areas. Using CO(2) laser stimulations, we analyzed the modifications induced by increasing thermal energy on evoked potentials recorded with electrodes implanted within SII and posterior insula in patients referred for presurgical evaluation of epilepsy. Although increasing stimulus intensities enhanced both SII and insular responses, the "dynamics" of their respective amplitude changes were different. SII responses were able to encode gradually the intensity of stimuli from sensory threshold up to a level next to pain threshold but tended to show a ceiling effect for higher painful intensities. In contrast, the posterior insular cortex failed to detect nonnoxious laser pulses but reliably encoded stimulus intensity variations at painful levels, without showing saturation effects for intensities above pain threshold. According to these results, one can assume that insular cortex could be more involved in the triggering of affective recognition of, and motor reaction to, noxious stimuli, whereas SII would be more dedicated to finer-grain discrimination of stimulus intensity, from nonpainful to painful levels.
185 citations
"Filtering the reality: Functional d..." refers result in this paper
...During wakefulness, LEP latencies were comparable to those reported in previous LEP studies using intracortical electrodes [e.g., Frot et al., 2007, 2008]....
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TL;DR: This study studies responses of the parieto-frontal opercular cortex to electric stimuli, as recorded by intra-cortical electrodes during stereotactic EEG presurgical assessment of patients with drug-resistant temporal lobe epilepsy and suggests the existence of dipolar SII sources radial to the scalp surface, which are overlooked in magnetic recordings.
Abstract: We studied responses of the parieto-frontal opercular cortex to electric stimuli, as recorded by intra-cortical electrodes during stereotactic EEG presurgical assessment of patients with drug-resistant temporal lobe epilepsy. After electrical stimulation of the median nerve at the wrist, we consistently recorded a negative-positive biphasic response peaking at 60 ms (N60) and 90 ms (P90) post-stimulus in the upper bank of the sylvian fissure contralateral to stimulation. Talairach stereotactic coordinates of the electrode contacts recording these responses covered the pre- and post-rolandic part of the upper bank of the sylvian fissure (25
175 citations
"Filtering the reality: Functional d..." refers background or methods in this paper
...Each contact and particularly those exhibiting the largest LEP amplitudes (Table I) were then localized in the Talairach space using their stereotactic coordinates: x for the lateral medial axis, with x 1⁄4 0 being the coordinate of the sagittal interhemispheric plane; y for the rostrocaudal (anterior–posterior) axis, y 1⁄4 0 being the coordinate of the vertical anterior commissure (VAC) plane, and z for the inferior–superior axis, z 1⁄4 0 being the coordinate of the horizontal anterior commissure–posterior commissure (AC–PC) plane [Frot and Mauguière, 1999]....
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...Coordinates of relevant targets were determined on the patient’s brain magnetic resonance (MR) images according to previously described procedures [Frot and Mauguière, 1999, 2003; Ostrowsky et al., 2002]....
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...…form the core of the so-called ‘‘Pain Matrix’’ (PM), or network of cortical structures that respond consistently to noxious mechanical or thermal stimuli [Apkarian et al., 2005; Frot and Mauguière, 1999; Garcia-Larrea et al., 2003; Lenz et al., 1998; Peyron et al., 1999; Treede et al., 1999]....
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...…plane; y for the rostrocaudal (anterior–posterior) axis, y ¼ 0 being the coordinate of the vertical anterior commissure (VAC) plane, and z for the inferior–superior axis, z ¼ 0 being the coordinate of the horizontal anterior commissure–posterior commissure (AC–PC) plane [Frot and Mauguière, 1999]....
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...In humans, these cortical areas form the core of the so-called ‘‘Pain Matrix’’ (PM), or network of cortical structures that respond consistently to noxious mechanical or thermal stimuli [Apkarian et al., 2005; Frot and Mauguière, 1999; Garcia-Larrea et al., 2003; Lenz et al., 1998; Peyron et al., 1999; Treede et al., 1999]....
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TL;DR: This study shows the existence of three distinct somatosensory maps in the suprasylvian, opercular and insular regions, and separate pain representations in SII andinsular cortex.
Abstract: Somatosensory and pain responses to direct intracerebral stimulations of the SII area were obtained in 14 patients referred for epilepsy surgery. Stimulations were delivered using transopercular electrodes exploring the parietal opercular cortex (SII area), the suprasylvian parietal cortex (SI area) and the insular cortex. SII responses were compared to those from adjacent SI and insular cortex. In the three areas we elicited mostly somatosensory responses, including paresthesiae, temperature and pain sensations. The rate of painful sensations (10%) was similar in SII and in the insula, while no painful sensation was evoked in SI. A few nonsomatosensory responses were evoked by SII stimulation. Conversely various types of non-somatosensory responses (auditory, vegetative, vestibular, olfacto-gustatory, etc.) were evoked only by insular stimulation, confirming that SII, like SI, are mostly devoted to the processing of somatosensory inputs whereas the insular cortex is a polymodal area. We also found differences in size and lateralization of skin projection fields of evoked sensations between the three studied areas, showing a spatial resolution of the somatotopic map in SII intermediate between those found in SI and insula. This study shows the existence of three distinct somatosensory maps in the suprasylvian, opercular and insular regions, and separate pain representations in SII and insular cortex.
170 citations
"Filtering the reality: Functional d..." refers methods in this paper
...This procedure aims at recording spontaneous seizures but also includes the functional mapping of potentially eloquent cortical areas using EPs recordings and cortical electrical stimulation [for a description of the stimulation procedure, see Mazzola et al., 2006; Ostrowsky et al., 2002]....
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TL;DR: Central pain resulting from posterior parasylvian lesions appears to be a distinct entity that can be identified unambiguously on the basis of clinical, radiological and electrophysiological data and is paradoxically closer to pain syndromes from brainstem lesions affecting selectively the spinothalamic pathways than to those caused by focal lesions of the posterior thalamus.
Abstract: Central pain with dissociated thermoalgesic sensory loss is common in spinal and brainstem syndromes but not in cortical lesions. Out of a series of 270 patients investigated because of somatosensory abnormalities, we identified five subjects presenting with central pain and pure thermoalgesic sensory loss contralateral to cortical stroke. All of the patients had involvement of the posterior insula and inner parietal operculum. Lemniscal sensory modalities (position sense, graphaestesia, stereognosis) and somatosensory evoked potentials to non-noxious inputs were always preserved, while thermal and pain sensations were profoundly altered, and laser-evoked potentials to thermo-nocoiceptive stimuli were always abnormal. Central pain resulting from posterior parasylvian lesions appears to be a distinct entity that can be identified unambiguously on the basis of clinical, radiological and electrophysiological data. It presents with predominant or isolated deficits for pain and temperature sensations, and is paradoxically closer to pain syndromes from brainstem lesions affecting selectively the spinothalamic pathways than to those caused by focal lesions of the posterior thalamus. The term 'pseudo-thalamic' is therefore inappropriate to describe it, and we propose parasylvian or operculo-insular pain as appropriate labels. Parasylvian pain may be extremely difficult to treat; the magnitude of pain-temperature sensory disturbances may be prognostic for its development, hence the importance of early sensory assessment with quantitative methods.
149 citations
"Filtering the reality: Functional d..." refers background in this paper
...The lateral subsystem includes afferents from the lateral thalamus to SI and operculo-insular cortices and is thought to encode intensity and localization of pain inputs [Apkarian et al., 2005; Garcia-Larrea et al., 2010; Peyron et al., 2000]....
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TL;DR: Observation of this clinical sequence at the onset of seizures on video-EEG recordings in TLE patients strongly suggests that the seizure-onset zone is located not in the temporal but in the insular lobe; recording directly from theinsular cortex should occur before making any decision regarding epilepsy surgery.
147 citations
"Filtering the reality: Functional d..." refers background in this paper
...…explore these areas resulted from the observation during scalp video-EEG recordings of ictal manifestations suggesting the possibility of seizures propagating to or originating from these regions [for a complete description of the rationale of electrode implantation, see Isnard et al., 2000, 2004]....
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