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.
Memories of painful events constitute the basis for assessing patients' pain. This study explores the brain oscillatory activity during short‐term memorization of a nociceptive stimulus. High‐density ...EEG activity (128 electrodes) was recorded in 13 healthy subjects during a match‐to‐sample sensory discrimination task, whereby participants compared the intensity of a thumb‐located electric shock (S2) with a prior stimulus to the same location (S1) delivered 8–10 s earlier. Stimuli were above or below the individual nociceptive threshold. EEG activity with intracortical source localization via LORETA source reconstruction was analysed during the inter‐stimuli period and contrasted with a non‐memory‐related control task.
The inter‐stimulus memorization phase was characterized by a focal alpha‐activity enhancement, significant during the nociceptive condition only, which progressed from bilateral occipital regions (cuneus and mid‐occipital gyri) during the first encoding—memorization phase towards the right‐superior and right mid‐temporal gyri during the 2–4 s immediately preceding S2. Initial alpha enhancement in occipital areas/cuneus is consistent with rapid non‐specific inhibition of task‐irrelevant visual processing during initial stimulus encoding. Its transfer to the right‐temporal regions was concomitant to the temporary upholding of the stimulus perceptual representation, previous to receiving S2, and suggests an active and local blockade of external interferences while these regions actively maintain internal information. These results add to a growing field indicating that alpha oscillations, while indicating local inhibitory processes, can also indirectly reveal active stimulus handling, including maintenance in short‐term memory buffers, by objectivizing the filtering out of irrelevant and potentially disrupting inputs in brain regions engaged in internally driven operations.
Local sleep spindles in the human thalamus Bastuji, Hélène; Lamouroux, Pierre; Villalba, Manon ...
Journal of physiology,
1 June 2020, 2020-06-00, 20200601, Letnik:
598, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Key points
Sleep spindles have recently been shown to occur not only across multiple neocortical regions but also locally in restricted cortical areas.
Here we show that local spindles are indeed ...present in the human posterior thalamus.
Thalamic local spindles had lower spectral power than non‐local ones.
While non‐local thalamic spindles had equal local and non‐local cortical counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site).
The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.
Sleep spindles are believed to subserve many sleep‐related functions, from memory consolidation to cortical development. Recent data using intracerebral recordings in humans have shown that they occur across multiple neocortical regions but may also be spatially restricted to specific brain areas (local spindles). The aim of this study was to characterize spindles at the level of the human posterior thalamus, with the hypothesis that, besides the global thalamic spindling activity usually observed, local spindles could also be present in the thalamus. Using intracranial, time‐frequency EEG recordings in 17 epileptic patients, we assessed the distribution of thalamic spindles during natural sleep stages N2 and N3 in six thalamic nuclei. Local spindles (i.e. spindles present in a single pair of recording contacts) were observed in all the thalamic regions explored, and compared with non‐local spindles in terms of intrinsic properties and cortical counterparts. Thalamic local and non‐local spindles did not differ in density, frequency or duration, but local spindles had lower spectral power than non‐local ones. Each thalamic spindle had a cortical counterpart. While non‐local thalamic spindles had equal cortical local and non‐local counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site). The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.
Key points
Sleep spindles have recently been shown to occur not only across multiple neocortical regions but also locally in restricted cortical areas.
Here we show that local spindles are indeed present in the human posterior thalamus.
Thalamic local spindles had lower spectral power than non‐local ones.
While non‐local thalamic spindles had equal local and non‐local cortical counterparts, local thalamic spindles had significantly more local cortical counterparts (i.e. occurring in a single cortical site).
The preferential association of local thalamic and cortical spindles supports the notion of thalamocortical loops functioning in a modular way.
Background and Objective
Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex provides supplementary relief for some individuals with chronic pain who are refractory to ...pharmacological treatment. As rTMS slowly enters treatment guidelines for pain relief, its starts to be confronted with challenges long known to pharmacological approaches: efficacy at the group‐level does not grant pain relief for a particular patient. In this review, we present and discuss a series of ongoing attempts to overcome this therapeutic challenge in a personalized medicine framework.
Databases and Data Treatment
Relevant scientific publications published in main databases such as PubMed and EMBASE from inception until March 2023 were systematically assessed, as well as a wide number of studies dedicated to the exploration of the mechanistic grounds of rTMS analgesic effects in humans, primates and rodents.
Results
The main strategies reported to personalize cortical neuromodulation are: (i) the use of rTMS to predict individual response to implanted motor cortex stimulation; (ii) modifications of motor cortex stimulation patterns; (iii) stimulation of extra‐motor targets; (iv) assessment of individual cortical networks and rhythms to personalize treatment; (v) deep sensory phenotyping; (vi) personalization of location, precision and intensity of motor rTMS. All approaches except (i) have so far low or moderate levels of evidence.
Conclusions
Although current evidence for most strategies under study remains at best moderate, the multiple mechanisms set up by cortical stimulation are an advantage over single‐target ‘clean’ drugs, as they can influence multiple pathophysiologic paths and offer multiple possibilities of individualization.
Significance
Non‐invasive neuromodulation is on the verge of personalised medicine. Strategies ranging from integration of detailed clinical phenotyping into treatment design to advanced patient neurophysiological characterisation are being actively explored and creating a framework for actual individualisation of care.
The interruption of sleep by a nociceptive stimulus is favoured by an increase in the pre‐stimulus functional connectivity between sensory and higher level cortical areas. In addition, stimuli ...inducing arousal also trigger a widespread electroencephalographic (EEG) response reflecting the coordinated activation of a large cortical network. Because functional connectivity between distant cortical areas is thought to be underpinned by trans‐thalamic connections involving associative thalamic nuclei, we investigated the possible involvement of one principal associative thalamic nucleus, the medial pulvinar (PuM), in the sleeper's responsiveness to nociceptive stimuli. Intra‐cortical and intra‐thalamic signals were analysed in 440 intracranial electroencephalographic (iEEG) segments during nocturnal sleep in eight epileptic patients receiving laser nociceptive stimuli. The spectral coherence between the PuM and 10 cortical regions grouped in networks was computed during 5 s before and 1 s after the nociceptive stimulus and contrasted according to the presence or absence of an arousal EEG response. Pre‐ and post‐stimulus phase coherence between the PuM and all cortical networks was significantly increased in instances of arousal, both during N2 and paradoxical (rapid eye movement REM) sleep. Thalamo‐cortical enhancement in coherence involved both sensory and higher level cortical networks and predominated in the pre‐stimulus period. The association between pre‐stimulus widespread increase in thalamo‐cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans‐thalamic transfer of information between cortical areas.
The interruption of sleep by a nociceptive stimulus is favoured by a pre‐stimulus increase in functional connectivity between the associative thalamus and both sensory and higher level cortical networks, as assessed by spectral EEG coherence. The association between pre‐stimulus thalamo‐cortical coherence and subsequent arousal suggests that the probability of sleep interruption by a noxious stimulus increases when it occurs during phases of enhanced trans‐thalamic transfer of information between cortical areas.
Remembering Prof. Manfred Zimmermann Handwerker, Hermann O.; Garcia‐Larrea, Luis
European journal of pain,
August 2024, 2024-08-00, 20240801, Letnik:
28, Številka:
7
Journal Article
Background
Innocuous cooling of the skin activates cold‐specific Aδ fibres, and hence, the recording of cold‐evoked potentials (CEPs) may improve the objective assessment of human thermo‐nociceptive ...function. While the feasibility of CEP recordings in healthy humans has been reported, their reliability and diagnostic use in clinical conditions have not been documented.
Methods
Here, we report the results of CEP recordings in 60 consecutive patients with suspected neuropathic pain, compared with laser‐evoked potentials (LEPs) which are the gold standard for thermo‐algesic instrumental assessment.
Results
CEP recording was a well‐tolerated procedure, with only ~15 min of surplus in exam duration. The reproducibility and signal‐to‐noise ratio of CEPs were lower than those of LEPs, in particular for distal lower limbs (LLs). While laser responses were interpretable in all patients, CEPs interpretation was inconclusive in 5/60 because of artefacts or lack of response on the unaffected side. Both techniques yielded concordant results in 73% of the patients. In 12 patients, CEPs yielded abnormal values while LEPs remained within normal limits; 3 of these patients had clinical symptoms limited to cold sensations, including cold‐heat transformation.
Conclusions
CEPs appear as a useful technique for exploring pain/temperature systems. Advantages are low cost of equipment and innocuity. Disadvantages are low signal‐to‐noise ratio for LL stimulation, and sensitivity to fatigue/habituation. Joint recording of CEPs and LEPs can increase the sensitivity of neurophysiological techniques to thin fibre‐ spinothalamic lesions, in particular, when abnormalities of cold perception predominate.
Significance
Recording of cold‐evoked potentials is a well‐tolerated, inexpensive and easy‐to‐use procedure that can be helpful in the diagnosis of abnormalities in the thin fibre‐ spinothalamic pathways. Supplementing LEPs with CEPs allows consolidating the diagnosis and, for some patients suffering from symptoms limited only to cold, CEPs but not LEPs may allow the diagnosis of thin fibre pathology. Optimal CEP recording conditions are important to overcome the low signal‐to‐noise ratio and habituation phenomena, which are less favourable than with LEPs.
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