Focal lesions induce large-scale percolation of sleep-like intracerebral activity in awake humans.

Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.

Hippocampal sleep spindles preceding neocortical sleep onset in humans.

The coexistence of regionally dissociated brain activity patterns -with some brain areas being active while other already showing sleep signs- may occur throughout all vigilance states including the transition from wakefulness to sleep and may account for both physiological as well as pathological events. These dissociated electrophysiological states are often characterized by multi-domain cognitive and behavioral impairment such as amnesia for events immediately preceding sleep. By performing simultaneous intracerebral electroencephalographic recordings from hippocampal as well as from distributed neocortical sites in neurosurgical patients, we observed that sleep spindles consistently occurred in the hippocampus several minutes before sleep onset. In addition, hippocampal spindle detections consistently preceded neocortical events, with increasing delays along the cortical antero-posterior axis. Our results support the notion that wakefulness and sleep are not mutually exclusive states, but rather part of a continuum resulting from the complex interaction between diffuse neuromodulatory systems and intrinsic properties of the different thalamocortical modules. This interaction may account for the occurrence of dissociated activity across different brain structures characterizing both physiological and pathological conditions.

Fluid boundaries between wake and sleep: experimental evidence from Stereo-EEG recordings.

Sleep and waking have been traditionally considered global behavioural states regulated by subcortical neuromodulatory circuits in a top-down fashion. Over the last years, we have been experiencing a paradigm shift towards a view that both wake and sleep are in essence local processes. Here we review recent clinical and basic research works supporting this view by taking advantage of stereotactic electroencephalography (Stereo-EEG, SEEG) recordings performed in epileptic patients. Specifically, we will discuss a growing body of evidence showing how electrophysiological features of sleep and wakefulness are coexisting across diffuse brain areas in pathological and physiological sleep as well as during state transitions (sleep onset and awakenings). Finally, we will discuss their implication for sleep medicine to extent that, reconsidering the classical definition of wakefulness and sleep as separate and mutually exclusive states may offer new insight for the understanding of parasomnias and other dissociated states.

TAAC - TMS Adaptable Auditory Control: A universal tool to mask TMS clicks.

BACKGROUND: Coupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones. NEW METHOD: Here we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains. RESULTS: We showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click. COMPARISON WITH EXISTING METHODS: Here, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines) and lower SPLs with respect to standard noises. CONCLUSIONS: At odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

Simultaneous stereo-EEG and high-density scalp EEG recordings to study the effects of intracerebral stimulation parameters.

BACKGROUND: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. OBJECTIVE: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. METHODS: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. RESULTS: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. CONCLUSIONS: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia.

OBJECTIVE: We examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia. METHODS: We prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement. RESULTS: CCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts. CONCLUSION: For the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus. SIGNIFICANCE: This intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.

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

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.