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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01 Jan 1968
2,439 citations
TL;DR: This article describes freely available software for presenting stereotaxically aligned patient scans and suggests that this technique of presenting lesions in terms of images normalized to standard stereOTaxic space should become the standard for neuropsychological studies.
Abstract: Traditionally lesion location has been reported using standard templates, text based descriptions or representative raw slices from the patient's CT or MRI scan. Each of these methods has drawbacks for the display of neuroanatomical data. One solution is to display MRI scans in the same stereotaxic space popular with researchers working in functional neuroimaging. Presenting brains in this format is useful as the slices correspond to the standard anatomical atlases used by neuroimagers. In addition, lesion position and volume are directly comparable across patients. This article describes freely available software for presenting stereotaxically aligned patient scans. This article focuses on MRI scans, but many of these tools are also applicable to other modalities (e.g. CT, PET and SPECT). We suggest that this technique of presenting lesions in terms of images normalized to standard stereotaxic space should become the standard for neuropsychological studies.
2,419 citations
"Filtering the reality: Functional d..." refers methods in this paper
...Anatomical localization of the cortical electrode contacts was counterchecked using fusion of skull X-ray after electrode implantation with the appropriate coronal MR slice of the patient’s brain (MRIcro software) [Rorden and Brett, 2000]....
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TL;DR: Data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control.
Abstract: Brain responses to pain, assessed through positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are reviewed. Functional activation of brain regions are thought to be reflected by increases in the regional cerebral blood flow (rCBF) in PET studies, and in the blood oxygen level dependent (BOLD) signal in fMRI. rCBF increases to noxious stimuli are almost constantly observed in second somatic (SII) and insular regions, and in the anterior cingulate cortex (ACC), and with slightly less consistency in the contralateral thalamus and the primary somatic area (SI). Activation of the lateral thalamus, SI, SII and insula are thought to be related to the sensory-discriminative aspects of pain processing. SI is activated in roughly half of the studies, and the probability of obtaining SI activation appears related to the total amount of body surface stimulated (spatial summation) and probably also by temporal summation and attention to the stimulus. In a number of studies, the thalamic response was bilateral, probably reflecting generalised arousal in reaction to pain. ACC does not seem to be involved in coding stimulus intensity or location but appears to participate in both the affective and attentional concomitants of pain sensation, as well as in response selection. ACC subdivisions activated by painful stimuli partially overlap those activated in orienting and target detection tasks, but are distinct from those activated in tests involving sustained attention (Stroop, etc.). In addition to ACC, increased blood flow in the posterior parietal and prefrontal cortices is thought to reflect attentional and memory networks activated by noxious stimulation. Less noted but frequent activation concerns motor-related areas such as the striatum, cerebellum and supplementary motor area, as well as regions involved in pain control such as the periaqueductal grey. In patients, chronic spontaneous pain is associated with decreased resting rCBF in contralateral thalamus, which may be reverted by analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. It is argued that imaging studies of allodynia should be encouraged in order to understand central reorganisations leading to abnormal cortical pain processing. A number of brain areas activated by acute pain, particularly the thalamus and anterior cingulate, also show increases in rCBF during analgesic procedures. Taken together, these data suggest that hemodynamic responses to pain reflect simultaneously the sensory, cognitive and affective dimensions of pain, and that the same structure may both respond to pain and participate in pain control. The precise biochemical nature of these mechanisms remains to be investigated.
2,113 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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...The lateral structures of the PM (posterior insula and suprasylvian operculum) are thought to subserve intensity coding and localization of pain inputs, while the medial PM system (anterior and mid-cingulate cortex) is linked to the attentional (orienting and arousing) components of pain [Apkarian et al., 2005; Dum et al., 2009; Frot et al., 2008; Peyron et al., 2000; Vogt, 2005]....
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...…to subserve intensity coding and localization of pain inputs, while the medial PM system (anterior and mid-cingulate cortex) is linked to the attentional (orienting and arousing) components of pain [Apkarian et al., 2005; Dum et al., 2009; Frot et al., 2008; Peyron et al., 2000; Vogt, 2005]....
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TL;DR: The affective dimension of pain is made up of feelings of unpleasantness and emotions associated with future implications, termed secondary affect, and experimental and clinical studies show serial interactions between pain sensation intensity, pain unpleasantness, and secondary affect.
Abstract: The affective dimension of pain is made up of feelings of unpleasantness and emotions associated with future implications, termed secondary affect. Experimental and clinical studies show serial interactions between pain sensation intensity, pain unpleasantness, and secondary affect. These pain dimensions and their interactions relate to a central network of brain structures that processes nociceptive information both in parallel and in series. Spinal pathways to limbic structures and medial thalamic nuclei provide direct inputs to brain areas involved in affect. Another source is from spinal pathways to somatosensory thalamic and cortical areas and then through a cortico-limbic pathway. The latter integrates nociceptive input with contextual information and memory to provide cognitive mediation of pain affect. Both direct and cortico-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional valence and response priorities.
1,892 citations
"Filtering the reality: Functional d..." refers background in this paper
...Indeed, although the thalamo-cingulate projections have been often considered to subserve affective components of the pain experience [e.g. Kulkarni et al., 2005; Price, 2000; Rainville et al., 1997], recent evidence in humans and monkeys shows that the spinothalamic input to anterior cingulate cortex (ACC) concern mainly, if not exclusively, cingulate regions primary involved in motor control, orienting and attention for action [Dum et al....
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...The finding of short-latency cingulate responses to pain suggests that the medial system is not exclusively devoted to slow affective processes [e.g., Price, 2000], but is also involved in fast reactions such as automatic orienting toward, and motor withdrawal from, pain stimuli....
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...…the thalamo-cingulate projections have been often considered to subserve affective components of the pain experience [e.g. Kulkarni et al., 2005; Price, 2000; Rainville et al., 1997], recent evidence in humans and monkeys shows that the spinothalamic input to anterior cingulate cortex (ACC)…...
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TL;DR: The progress made in understanding the insula in the decade following an earlier review is examined and confirmation has been given to theinsula as a visceral sensory area, visceral motor area, motor association area, vestibular area, and language area.
1,685 citations
"Filtering the reality: Functional d..." refers background in this paper
...…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…...
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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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