Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients

Rosanova, Mario; Fecchio, Matteo; Casarotto, Silvia; Sarasso, Simone; Casali, Adenauer G.; Pigorini, Andrea; Comanducci, Angela; Seregni, Francesca; Devalle, Guya; Citerio, Giuseppe; Bodart, Olivier; Boly, Mélanie; Gosseries, Olivia; Laureys, Steven; Massimini, Marcello

doi:10.1038/s41467-018-06871-1

Cited by 132 publications

(200 citation statements)

References 75 publications

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“…However, due to its activity-dependent nature, cortical bistability and the associated OFF-periods can be better revealed using a perturbational approach, whereby the impulse-response properties of cortical neurons are challenged by means of direct activations (22,23). Consistently, TMSevoked EEG events similar to those reported here were previously found in sleeping (25,44,45) and anesthetized (46,47) healthy controls and never in healthy awake subjects (25,28).…”

Section: Discussionsupporting

confidence: 84%

“…a significant suppression of high frequency (>20 Hz) EEG power compared to baseline (19,20,26) confined to the perilesional stimulated site ( Figure 1B,C and D). Furthermore, we aimed at assessing the effects of local cortical OFF-periods on local signal complexity as measured by the adaptation of a recently proposed index of perturbational complexity (PCI st ; (27)) TMS reveals local, sleep-like cortical OFF-periods over the affected hemisphere only in patients with corticosubcortical lesions irrespective of the etiology In the MCA ischemia group, TMS-evoked EEG potentials (TEPs) obtained from the stimulation of the contralesional site were low-amplitude, fast-frequency recurrent scalp waves similar to those previously observed in healthy awake individuals (Figure1B and Figure 2A, red trace; (25,28)). When TMS was applied using the same stimulation parameters over the perilesional site, TEPs were characterized by a local slow EEG potential ( Figure 1B, C and 2A, blue traces) associated with an initial broad-band activation followed by a significant suppression of high frequency EEG power starting roughly at 150 ms after TMS (mean±SEM: 167±14 ms) over the four channels closest to the stimulation site ( Figure 1B and C).…”

Section: Resultssupporting

confidence: 73%

“…In this context, increasing evidence suggest that additional symptoms following brain injury actually result from the local functional disruption in intact brain areas anatomically and functionally connected to those affected by the insult (1)(2)(3)(4)(5). In an extreme case, the ubiquitous presence of pathological OFF-periods in response to TMS across cortical islands spared by anatomical lesions in awake VS/UWS patients was shown to prevent the build-up of global complexity, resulting in behavioral unresponsiveness (25,29,30). Here, we report for the first time the presence of three different local patterns of cortical reactivity within the same patient ( Figure S4).…”

Section: Discussionmentioning

confidence: 99%

“…Most important, a follow-up study showed that the same events can be detected non-invasively by applying transcranial magnetic stimulation (TMS) combined with EEG (TMS/EEG). Specifically, multisite TMS in healthy sleeping individuals as well as in unresponsive wakefulness syndrome (UWS) patients showed the ubiquitous occurrence of OFF-periods leading to a global impairment of causality and brain complexity (25).…”

Section: Introductionmentioning

confidence: 99%

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Local sleep-like cortical reactivity in the awake brain after focal injury

Sarasso

D’Ambrosio

Fecchio

et al. 2019

Preprint

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One Sentence Summary: Focal cortical injuries are associated with local intrusion of sleep-like dynamics over the perilesional areas which disrupt local signal complexity and coexist with typical wakefulness cortical reactivity patterns within the same brain. AbstractThe functional consequences of brain injury are known to depend on neuronal alterations extending beyond the area of structural damage. Although a lateralized EEG slowing over the injured hemisphere was known since the early days of clinical neurophysiology, its electrophysiological mechanisms were not systematically investigated. In parallel, basic sleep research has thoroughly characterized the neuronal events underlying EEG slow waves in physiological conditions. These EEG events reflect brief interruptions of neuronal firing (OFF-periods) that can occur locally and have prominent consequences on network and behavioral functions. Notably, the EEG slow waves observed following focal brain injury have been never explicitly connected to local sleep-like neuronal events. In previous works, probing cortical circuits with transcranial magnetic stimulation coupled with EEG (TMS/EEG) proved as an effective way to reveal the tendency of cortical circuits to transiently plunge into silent OFF-periods. Here, using this approach, we show that the intact cortex surrounding focal brain injuries engages locally in pathological sleep-like dynamics. Specifically, we employed TMS/EEG in a cohort of thirty conscious awake patients with chronic focal and multifocal brain injuries of various etiologies. TMS systematically evoked prominent slow waves associated with sleep-like OFF-periods in the area surrounding focal cortico-subcortical lesions. These events were associated with a local disruption of signal complexity and were absent when stimulating the contralateral hemisphere. Perilesional sleep-like OFF-periods may represent a valid read-out of the electrophysiological state of discrete cortical circuits following brain injury as well as a potential target of interventions aimed at fostering functional recovery.

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Section: Discussionsupporting

confidence: 84%

Section: Resultssupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Local sleep-like cortical reactivity in the awake brain after focal injury

Sarasso

D’Ambrosio

Fecchio

et al. 2019

Preprint

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“…Indeed, slow oscillations are a hallmark of pathological unconscious states, found in severely brain injured patients and vegetative state patients . In such patients, dis- ruption of causality and complexity in response to transcranial magnetic stimulation [Rosanova et al, 2018] appears consistent with anesthesia-type slow waves, suggesting adaptation-like mechanisms could play a critical role in impairing information representation. Furthermore, deceleration of slow oscillatory patterns during SWS [Mander et al, 2016, Castano-Prat et al, 2017 and loss of memory [Prinz et al, 1982] are also biomarkers of Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 76%

Cholinergic switch between two types of slow waves in cerebral cortex

Nghiem

Tort-Colet

Górski

et al. 2018

Preprint

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Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory vs excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

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