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.

EEG spectral exponent as a synthetic index for the longitudinal assessment of stroke recovery.

OBJECTIVE: Quantitative Electroencephalography (qEEG) can capture changes in brain activity following stroke. qEEG metrics traditionally focus on oscillatory activity, however recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. We assessed neurophysiological alterations and recovery after mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD). METHODS: Eighteen patients (n = 18) with mild to moderate mono-hemispheric Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n = 16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients. RESULTS: At T0, stroke patients showed significantly more negative SE values than HC (p = 0.003), reflecting broad-band EEG slowing. Most important, in patients SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1. This SE renormalization significantly correlated with National Institute of Health Stroke Scale (NIHSS) improvement (R = 0.63, p = 0.005). CONCLUSIONS: SE is a reliable readout of the neurophysiological and clinical alterations occurring after an ischaemic cortical lesion. SIGNIFICANCE: SE promise to be a robust method to monitor and predict patients' functional outcome.

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.

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.

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.

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.

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.

Cortical mechanisms of loss of consciousness: insight from TMS/EEG studies.

In a recent series of experiments we recorded the electroencephalogram (EEG) response to a direct cortical stimulation in humans during wakefulness, NREM sleep, REM sleep and anesthesia by means of a combination of transcranial magnetic stimulation (TMS) and high-density EEG (hd-EEG). TMS/hd-EEG measurements showed that, while during wakefulness and REM sleep the brain is able to sustain long-range specific patterns of activation, during NREM sleep and Midazolam-induced anesthesia, when consciousness fades, this ability is lot: the thalamocortical system, despite being active and reactive, either breaks down in causally independent modules (producing a local slow wave), or it bursts into an explosive and non-specific response (producing a global EEG slow wave). We hypothesize that, like spontaneous sleep slow waves, the slow waves triggered by TMS during sleep and anaesthesia are due to bistability between upand down-states in thalamocortical circuits. In this condition, the inescapable occurrence of a silent, down state after an initial activation impairs the ability of thalamocortical circuits to sustain long-range, differentiated patterns of activation, a theoretical requisite for consciousness. According to animal experiments and computer simulations, thalamocortical bistability may result from increased K-currents, from alterations of the balance between excitation and inhibition and from partial cortical de-afferentation. We hypothesize that these factor may play an important role in determining loss, and recovery, of consciousness also in brain-injured subjects. If this is the case, some types of brain lesions may impair information transmission, above and beyond the associated anatomical disconnection, by inducing bistability in portions of the thalamocortical system that are otherwise healthy.

Overnight changes in waking auditory evoked potential amplitude reflect altered sleep homeostasis in major depression.

OBJECTIVE: Sleep homeostasis is altered in major depressive disorder (MDD). Pre- to postsleep decline in waking auditory evoked potential (AEP) amplitude has been correlated with sleep slow wave activity (SWA), suggesting that overnight changes in waking AEP amplitude are homeostatically regulated in healthy individuals. This study investigated whether the overnight change in waking AEP amplitude and its relation to SWA is altered in MDD. METHOD: Using 256-channel high-density electroencephalography, all-night sleep polysomnography and single-tone waking AEPs pre- and postsleep were collected in 15 healthy controls (HC) and 15 non-medicated individuals with MDD. RESULTS: N1 and P2 amplitudes of the waking AEP declined after sleep in the HC group, but not in MDD. The reduction in N1 amplitude also correlated with fronto-central SWA in the HC group, but a comparable relationship was not found in MDD, despite equivalent SWA between groups. No pre- to postsleep differences were found for N1 or P2 latencies in either group. These findings were not confounded by varying levels of alertness or differences in sleep variables between groups. CONCLUSION: MDD involves altered sleep homeostasis as measured by the overnight change in waking AEP amplitude. Future research is required to determine the clinical implications of these findings.

Electrophysiological traces of visuomotor learning and their renormalization after sleep.

OBJECTIVE: Adapting movements to a visual rotation involves the activation of right posterior parietal areas. Further performance improvement requires an increase of slow wave activity in subsequent sleep in the same areas. Here we ascertained whether a post-learning trace is present in wake EEG and whether such a trace is influenced by sleep slow waves. METHODS: In two separate sessions, we recorded high-density EEG in 17 healthy subjects before and after a visuomotor rotation task, which was performed both before and after sleep. High-density EEG was recorded also during sleep. One session aimed to suppress sleep slow waves, while the other session served as a control. RESULTS: After learning, we found a trace in the eyes-open wake EEG as a local, parietal decrease in alpha power. After the control night, this trace returned to baseline levels, but it failed to do so after slow wave deprivation. The overnight change of the trace correlated with the dissipation of low frequency (<8 Hz) NREM sleep activity only in the control session. CONCLUSIONS: Visuomotor learning leaves a trace in the wake EEG alpha power that appears to be renormalized by sleep slow waves. SIGNIFICANCE: These findings link visuomotor learning to regional changes in wake EEG and sleep homeostasis.

Non-fluent aphasia and neural reorganization after speech therapy: insights from human sleep electrophysiology and functional magnetic resonance imaging.

Stroke is associated with long-term functional deficits. Behavioral interventions are often effective in promoting functional recovery and plastic changes. Recent studies in normal subjects have shown that sleep, and particularly slow wave activity (SWA), is tied to local brain plasticity and may be used as a sensitive marker of local cortical reorganization after stroke. In a pilot study, we assessed the local changes induced by a single exposure to a therapeutic session of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects), a behavioral therapy used for recovery in patients with post-stroke aphasia. In addition, we measured brain activity changes with functional magnetic resonance imaging (fMRI) in a language observation task before, during and after the full IMITATE rehabilitative program. Speech production improved both after a single exposure and the full therapy program as measured by the Western Aphasia Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization in functionally-connected, speech-relevant areas in the left hemisphere. These preliminary results suggest that sleep hd-EEGs, and the topographical analysis of SWA parameters, are well suited to investigate brain plastic changes underpinning functional recovery in neurological disorders.