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: This work discusses neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition, and indicates possible roles for sleep in neuroplasticity.
Abstract: Sleep can be addressed across the entire hierarchy of biological organization. We discuss neuronal-network and regional forebrain activity during sleep, and its consequences for consciousness and cognition. Complex interactions in thalamocortical circuits maintain the electroencephalographic oscillations of non-rapid eye movement (NREM) sleep. Functional neuroimaging affords views of the human brain in both NREM and REM sleep, and has informed new concepts of the neural basis of dreaming during REM sleep — a state that is characterized by illogic, hallucinosis and emotionality compared with waking. Replay of waking neuronal activity during sleep in the rodent hippocampus and in functional images of human brains indicates possible roles for sleep in neuroplasticity. Different forms and stages of learning and memory might benefit from different stages of sleep and be subserved by different forebrain regions.
746 citations
"Filtering the reality: Functional d..." refers background in this paper
...…increased metabolism in the mid- and anterior cingulate during paradoxical sleep as compared to resting wakefulness [Braun et al., 1997; Maquet et al., 1996; Nofzinger et al., 1997], and this has been related to emotional features in dreams [Hobson and Pace-Schott, 2002; Maquet et al. 2000]....
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..., 1997], and this has been related to emotional features in dreams [Hobson and Pace-Schott, 2002; Maquet et al. 2000]....
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TL;DR: Using positron emission tomography and regional cerebral blood flow measurements, it is shown that waking experience influences regional brain activity during subsequent sleep and supports the hypothesis that memory traces are processed during REM sleep in humans.
Abstract: The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.
706 citations
"Filtering the reality: Functional d..." refers background in this paper
...Painful events can be incorporated into ongoing dreams [Maury, 1861; Raymond et al., 2002], and recent work using scalp-recorded evoked potentials (EPs) has confirmed the persistence of sizeable cortical Contract grant sponsors: French National Agency for Medical Research (INSERM), Fondation pour…...
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...…it remains surprising that (i) painful stimuli can be incorporated onto dreams, or even trigger them, without necessarily awakening the subject [Maury, 1861; Nielsen et al., 1993; Raymond et al., 2002] and (ii) up to 70% of stimuli at nociceptive threshold can evoke cortical EPs [Bastuji et…...
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01 Jan 1997
633 citations
"Filtering the reality: Functional d..." refers background in this paper
...PET-scan studies have reported increased metabolism in the mid- and anterior cingulate during paradoxical sleep as compared to resting wakefulness [Braun et al., 1997; Maquet et al., 1996; Nofzinger et al., 1997], and this has been related to emotional features in dreams [Hobson and Pace-Schott,…...
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TL;DR: Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.
Abstract: Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6°C) or low (mean 39°C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. Only the insular/second somatosensory cortices were found to respond whatever the attentional context and might, therefore, subserve the sensory-discriminative dimension of pain ( intensity coding ). In parallel, other rCBF changes previously described as `pain-related' appeared to depend essentially on the attentional context. Attention to the thermal stimulus involved a large network which was primarily right-sided, including prefrontal, posterior parietal, anterior cingulate cortices and thalamus. Anterior cingulate activity was not found to pertain to the intensity coding network but rather to the attentional neural activity triggered by pain. The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.
583 citations
"Filtering the reality: Functional d..." refers background in this paper
...…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: It is concluded that there is a specific thalamic nucleus for pain and temperature sensation in both monkey and human that fit clinical descriptions of the pain-producing region in humans.
Abstract: THE existence of a posterolateral thalamic relay nucleus for pain and temperature sensation was postulated in 1911, on the basis of the stroke-induced analgesia and thermanaesthesia found paradox-ically in patients with thalamic pain syndrome1. Pain or tempera-ture sensations can be evoked in humans by electrical stimulation in a vaguely defined region of the posterolateral thalamus2'3. Here we use anterograde tracing and single unit recordings to demon-strate that there is a distinct nucleus in the posterior thalamus of the macaque monkey that receives a dense, topographic input from spinothalamic lamina I neurons and in which almost all neurons are nociceptive- or thermoreceptive-specific. Immunohistochemical staining showed that this nucleus is defined by a dense calbindin-positive fibre plexus in the macaque, so we applied the same stain-ing method to sections of human thalamus. We found a nearly identical fibre plexus localized within a distinct nucleus that is cytoarchitectonically homologous to the lamina I relay nucleus in the macaque thalamus. The stereotaxic coordinates of this nucleus and its location relative to the main somatosensory representation fit clinical descriptions of the pain-producing region in humans. We conclude that this is a specific thalamic nucleus for pain and temperature sensation in both monkey and human.
552 citations
"Filtering the reality: Functional d..." refers background in this paper
...…nuclei: ventral posterior group (VPL/VPM/VPI), posterior nuclei (Po) and posterior part of the ventral medial nucleus (VMpo) [Augustine, 1996; Craig et al., 1994; Freidman and Murray, 1986; Kobayashi et al., 2009; Montes et al., 2005; Stevens et al., 1993], whereas the cingulate cortex…...
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...The operculo-insular cortices receive afferents essentially from lateral thalamic nuclei: ventral posterior group (VPL/VPM/VPI), posterior nuclei (Po) and posterior part of the ventral medial nucleus (VMpo) [Augustine, 1996; Craig et al., 1994; Freidman and Murray, 1986; Kobayashi et al., 2009; Montes et al., 2005; Stevens et al., 1993], whereas the cingulate cortex (Brodmann’ area 24) receives direct projections from midline and intralaminar thalamic nuclei that are themselves the target of spinothalamic afferents [Baleydier and Mauguière, 1980; Hatanaka et al....
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