Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

Pigorini, Andrea; Sarasso, Simone; Proserpio, Paola; Szymanski, Caroline; Arnulfo, Gabriele; Casarotto, Silvia; Fecchio, Matteo; Rosanova, Mario; Mariotti, Maurizio; Russo, Giorgio Lo; Palva, J. Matias; Nobili, Lino; Massimini, Marcello

doi:10.1016/j.neuroimage.2015.02.056

Cited by 171 publications

(245 citation statements)

References 58 publications

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“…A potential explanation for the increased stimulation responses could be the intrinsic tendency of cortical neurons to fall into a down state after a transient activation during non-rapid eye movement sleep, as recently discussed in ref. 31. The overall steady levels of cortical stimulation markers in the long term observed here as well as in ref.…”

Section: Discussionsupporting

confidence: 76%

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Meisel

Schulze‐Bonhage

Freestone

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

112

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Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.excitability | epilepsy | sleep N ormal functioning of cortical networks critically depends on a finely tuned level of excitability, the transient or steady-state response in which the brain reacts to a stimulus. Whereas small, local responses indicate a comparably small excitability, large and global responses consequently suggest excitability to be high. The importance of adequate excitability levels is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability. In epilepsy, changes in cortical network excitability are believed to be an important cause underlying the initiation and spread of seizures, that is, the large nonphysiological neuronal activity events across time and space (1-3). Evidence for changes of excitability in brain networks affected in epilepsy has come from a variety of observations. To assess the level of excitability under in vivo experimental conditions one usually measures the size of the evoked cortical activity to external perturbations, typically either by transcranial magnetic stimulation (TMS) or, in the case of epilepsy patients, by electrical stimulation. Studies of electrical stimulation with subdural electrodes during interictal periods found the evoked potentials to be larger in regions related to the cortical onset region of epileptiform activity (4-6). The enhanced responses to electrical stimulation in epileptogenic cortex were taken as indication of an increased excitability of neural tissue in these areas. Similarly, studies using TMS consistently reported a hyperexcitability in focal epilepsies (7-10). Consequently, changes in excitability have been helpful in identifying the se...

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Section: Discussionsupporting

confidence: 76%

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Meisel

Schulze‐Bonhage

Freestone

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

112

View full text Add to dashboard Cite

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“…long-range temporal correlations [14]) and rapidly vanishing responses to direct magnetic and electric stimulation of the cortex [28][29][30]38]. Within our framework, both arise as a result of increased stability, with endogenous as well as exogenous fluctuations failing to displace the system between different metastable states.…”

Section: Discussionmentioning

confidence: 96%

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Tagliazucchi

Chialvo

Siniatchkin

et al. 2016

J. R. Soc. Interface.

179

187

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Loss of cortical integration and changes in the dynamics of electrophysiological brain signals characterize the transition from wakefulness towards unconsciousness. In this study, we arrive at a basic model explaining these observations based on the theory of phase transitions in complex systems. We studied the link between spatial and temporal correlations of large-scale brain activity recorded with functional magnetic resonance imaging during wakefulness, propofol-induced sedation and loss of consciousness and during the subsequent recovery. We observed that during unconsciousness activity in frontothalamic regions exhibited a reduction of long-range temporal correlations and a departure of functional connectivity from anatomical constraints. A model of a system exhibiting a phase transition reproduced our findings, as well as the diminished sensitivity of the cortex to external perturbations during unconsciousness. This framework unifies different observations about brain activity during unconsciousness and predicts that the principles we identified are universal and independent from its causes.

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“…This may happen, for example, following changes in the neuromodulatory milieu, when potassium currents are abnormally increased and when the balance between excitation and inhibition is disrupted 43, 44. In this regard, it is worth recalling that low complexity responses to cortical stimulation are the rule during states such as anesthesia18 and NREM sleep,45 when bistability is present but can be readily reversed 46…”

Section: Discussionmentioning

confidence: 99%

Stratification of unresponsive patients by an independently validated index of brain complexity

Casarotto

Comanducci

Rosanova

et al. 2016

Annals of Neurology

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371

436

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ObjectiveValidating objective, brain‐based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness—the Perturbational Complexity Index (PCI)—in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs).MethodsThe benchmark population encompassed 150 healthy controls and communicative brain‐injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]).ResultsWe found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition.InterpretationGiven its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high‐PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718–729

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Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

Cited by 171 publications

References 58 publications

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle

Large-scale signatures of unconsciousness are consistent with a departure from critical dynamics

Stratification of unresponsive patients by an independently validated index of brain complexity

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