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TMS-evoked cortical responses in Group I patients. A group of five vegetative state (VS, A), five minimally conscious state (MCS, B), and two patients with locked-in syndrome (LIS, C) underwent one TMS/EEG session after 7 days of repeated evaluations by means of the CRS-R. For each patient, the averaged TMS-evoked potentials recorded at one electrode under the stimulator (black trace) and the respective significance threshold (upper and lower boundaries of the pink bands; bootstrap statistics, P 5 0.01) are shown. The sources involved by maximum cortical currents (10 most active sources) during the significant post-stimulus period of the global mean field power are plotted on the cortical surface and colour-coded according to their location in six anatomical macro-areas as indicated in the legend; the number of detected sources is indicated at the top right of each map. The time-series (colored traces) represent TMS-evoked cortical currents recorded from an array of six sources (black circles on the cortical map in the legend) located $2 cm lateral to the midline, one for each macro-area (Supplementary Fig. 1). The white crosses mark the sites of stimulation. For all patients, the responses to the left parietal cortex stimulation are shown, except for one patient (Patient 5) in whom a significant response could only be detected in the right hemisphere (Supplementary Fig. 2). EEG positivity is upward. L = left; R = right.
Source publication
Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some d...
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Context 1
... in previous TMS/EEG works performed during sleep (Massimini et al., 2005(Massimini et al., , 2007, we considered only the cortical activations that corresponded to significant GMFP values (see Supplementary Fig. 1 for a graphical example). To assess the threshold for significance ( Supplementary Fig. 1), a bootstrap method ( Delorme and Makeig, 2004;Lv et al., 2007;McCubbin et al., 2008), which does not assume normal distribution of the observations, was applied by shuf- fling the time samples of GMFP prestimulus activity (from À300 to À 50 ms) at the single-trial level and by calculating 500 surrogated prestimulus GMFP time-series. ...
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... in previous TMS/EEG works performed during sleep (Massimini et al., 2005(Massimini et al., , 2007, we considered only the cortical activations that corresponded to significant GMFP values (see Supplementary Fig. 1 for a graphical example). To assess the threshold for significance ( Supplementary Fig. 1), a bootstrap method ( Delorme and Makeig, 2004;Lv et al., 2007;McCubbin et al., 2008), which does not assume normal distribution of the observations, was applied by shuf- fling the time samples of GMFP prestimulus activity (from À300 to À 50 ms) at the single-trial level and by calculating 500 surrogated prestimulus GMFP time-series. From each random realization, the maximum value across all latencies was selected to obtain a maximum distribution (control for type I error) and significance level was set at P 5 0.01. ...
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... each significant latency of the post-stimulus GMFP, the location of maximum neuronal current (10 most active sources) was detected on the cortical surface. Plotting and counting the sources involved by maximum neuronal currents across all significant time points in the first 300 ms post-stimulus resulted in the cortical maps and in the values reported in Figs 1-3 and Supplementary Figs 1-3 and 5. ...
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... each significant latency of the post-stimulus GMFP, the location of maximum neuronal current (10 most active sources) was detected on the cortical surface. Plotting and counting the sources involved by maximum neuronal currents across all significant time points in the first 300 ms post-stimulus resulted in the cortical maps and in the values reported in Figs 1-3 and Supplementary Figs 1-3 and 5. ...
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... area during the entire post-stimulus period. On the contrary, the number of detected sources is large if TMS triggers maximum cortical currents that involve different cor- tical areas at different times. In order to describe the time course of TMS-evoked cortical activations in different areas, the currents from a grid of six cortical sources ( Fig. 1 ...
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... I) underwent a TMS/EEG session after 1 week of repeated behavioural evalu- ations by means of the CRS-R ( Giacino et al., 2004). Five subjects from this group showed only reflexive behaviour, remained unre- sponsive to the environment during the whole observation period and were diagnosed in a vegetative state (Supplementary Table 1). As shown in Fig. 1A and Supplementary Fig. 2A, TMS evoked a slow, positive-negative EEG response in all patients in a vegetative state except for one anoxic patient (Patient 4) in whom no re- sponse could be elicited even when TMS was delivered at high intensity (200 V/m) in both hemispheres (Supplementary Fig. 2A and 4). The coloured maps show, for each ...
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... shown in Fig. 1A and Supplementary Fig. 2A, TMS evoked a slow, positive-negative EEG response in all patients in a vegetative state except for one anoxic patient (Patient 4) in whom no re- sponse could be elicited even when TMS was delivered at high intensity (200 V/m) in both hemispheres (Supplementary Fig. 2A and 4). The coloured maps show, for each subject, the cortical sources that were involved by TMS-evoked maximum neuronal currents during the significant intervals of the post-stimulus period (0-300 ms) (see 'Materials and methods' section and Supplementary Fig. 1 for details about the statistical procedure). At the right side of each map the number of detected sources is reported together with the time series of neuronal currents re- corded from six selected cortical areas (Supplementary Fig. 1). ...
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... coloured maps show, for each subject, the cortical sources that were involved by TMS-evoked maximum neuronal currents during the significant intervals of the post-stimulus period (0-300 ms) (see 'Materials and methods' section and Supplementary Fig. 1 for details about the statistical procedure). At the right side of each map the number of detected sources is reported together with the time series of neuronal currents re- corded from six selected cortical areas (Supplementary Fig. 1). In all patients in a vegetative state, TMS elicited maximum cortical currents that remained localized during the entire significant post-stimulus period, involving a small number of sources around the stimulated area. ...
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... pursuit or responses to simple commands) but were unable to communicate reliably with the examiners. In these cases, TMS invariably triggered a complex EEG response associated with a rapidly changing pattern of cortical activation, where maximum neuronal currents shifted over time from the stimulated site to a large number of distant sources ( Fig. 1B and Supplementary Fig. 2B). This pattern contrasted starkly with the local, simple wave recorded in patients in a vegetative state and was, instead, comparable to the one obtained in two subjects with locked-in syndrome (Fig. 1C and Supplementary Fig. 2C). Subjects with locked-in syndrome, though being largely paralysed at the time of recording, could signal ...
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... where maximum neuronal currents shifted over time from the stimulated site to a large number of distant sources ( Fig. 1B and Supplementary Fig. 2B). This pattern contrasted starkly with the local, simple wave recorded in patients in a vegetative state and was, instead, comparable to the one obtained in two subjects with locked-in syndrome (Fig. 1C and Supplementary Fig. 2C). Subjects with locked-in syndrome, though being largely paralysed at the time of recording, could signal that they were fully aware through vertical eye movements. In Fig. 3 the number of sources involved by the propagation of TMS-evoked maximum currents (effective connectivity) is reported for all TMS/EEG sessions (Fig. 3A), all ...
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... sources involved by maximum cortical currents (10 most active sources) during the significant post-stimulus period of the global mean field power are plotted on the cortical surface and colour-coded according to their location in six anatomical macro-areas as indicated in the legend; the number of detected sources is indicated at the top right of each map. The time-series (colored traces) represent TMS-evoked cortical currents recorded from an array of six sources (black circles on the cortical map in the legend) located $2 cm lateral to the midline, one for each macro-area ( Supplementary Fig. 1). The white crosses mark the sites of stimulation. ...
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... electrode under the stimulator are shown. The cor- responding spread and the time-course of the cortical currents evoked by TMS is measured. The sources involved by maximum neuronal currents during the significant post-stimulus period are plotted on the cortical surface and colour-coded according to their location in six anatomical macro-areas (Fig. 1); the number of detected sources is indicated at the top right of each map. The time-series represent TMS-evoked cortical currents recorded from an array of six sources (see their locations in Fig. 1) located $2 cm lateral to the midline, one for each macro-area. The white crosses mark the sites of stimulation; in each patient, the left ...
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... the significant post-stimulus period are plotted on the cortical surface and colour-coded according to their location in six anatomical macro-areas (Fig. 1); the number of detected sources is indicated at the top right of each map. The time-series represent TMS-evoked cortical currents recorded from an array of six sources (see their locations in Fig. 1) located $2 cm lateral to the midline, one for each macro-area. The white crosses mark the sites of stimulation; in each patient, the left parietal cortex was stimulated when patients entered a vegetative state from coma (Session 1), soon after transition to a minimally conscious state or at least 30 days of permanence in a vegetative ...
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... connectivity was null in the two anoxic subjects (Patient 4 from Group I and Patient 17 from Group II). environment is challenging by definition, since, in these cases, there is no behavioural reference to assess the presence of con- sciousness. In an attempt to overcome this circularity, we have previously tested TMS/EEG measures in states in which consciousness is unambiguously present [alert wakefulness (Massimini et al., 2005), dreaming ] or unambiguously reduced [early slow wave sleep ( Massimini et al., 2005), general anaesthesia (Ferrarelli et al., 2010)]. Here, we Figure 4 EEG spectra show evident changes from minimally conscious state (MCS) to emergence from minimally conscious state (EMCS) but not from vegetative state (VS) to minimally conscious state. ...
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... patients in a vegetative state caused by anoxia (Patients 4 and 17) no significant EEG responses could be elicited, even when TMS was delivered at high intensity at multiple stimulation sites ( Fig. 3 and Supplementary Fig. 4), consist- ent with an extensive necrosis of the cerebral cortex (Kinney and Samuels, 1994). In non-anoxic patients in a vegetative state TMS elicited, at both frontal and parietal sites, a strong response that remained local (Figs 1, 2, Supplementary Fig. 2 and 3) corroborating the notion that the brain of these patients may retain islands of cortex (including associative areas) that are responsive, but recipro- cally disconnected ( Schiff et al., 2002;Laureys et al., 2004). According to post-mortem ( Adams et al., 2000) and in vivo (Fernandez-Espejo et al., 2011) neuropathological studies, this dis- connection is primarily structural and may be largely due to wide- spread injury of cortico-cortical fibres but also to thalamic damage, leading to a substantial impairment of cortico-thalamo-cortical cir- cuits. ...
Citations
... Транскраниальная магнитная стимуляция (ТМС)метод неинвазивной стимуляции коры головного мозга с помощью переменного магнитного поля. В диагностике пациентов с нарушениями сознания сочетание навигационной ТМС и многоканальной ЭЭГ применяется для оценки эффективности коннективности и корковой возбудимости, что позволяет дифференцировать паттерны активации головного мозга у пациентов в ВС/САБ и при синдроме «запертого человека» [40]. Количественная оценка влияния импульса ТМС на активность головного мозга позволяет различать уровни сознания как у здоровых субъектов (во время сна и анестезии), так и у пациентов с нарушением сознания [1,[41][42][43][44][45]. ...
The relevance of the problem under consideration is determined by the need to develop and improve interdisciplinary approaches to the diagnosis and rehabilitation of disorders of consciousness in patients with brain pathology. The purpose of the article is an analytical review of the methods of neuropsychological and neurophysiological diagnostics and rehabilitation work with patients in reduced states of consciousness. The results of the review. It is noted that the neuropsychological content of the concept of "consciousness" is insufficiently developed and there is no unified point of view on the brain basis of consciousness, as well as on methodological and procedural limitations that arise when a neuropsychologist works with patients in a vegetative state of consciousness and in a state of minimal consciousness. The problem of consistency of the results of behavioral (neuropsychological) and instrumental (neurophysiological) methods for assessing the level of states of consciousness conducted by different specialists (neuropsychologists, neurologists, neurophysiologists) who are part of a multidisciplinary team is considered. The possibility of combining the procedure of neuropsychological examination and instrumental (neurophysiological) methods in the diagnosis of patients in a vegetative state of consciousness, in a state of minimal consciousness) and the prognosis of restoring the level of consciousness is analyzed. Conclusion. The possibility of an integrated approach to the diagnosis of a state of consciousness associated with a combination of behavioral (observation-based) and objective (instrumental) research methods is confirmed, and possible ways of its implementation are considered.
... • A healthy-like spectrum increases the likelihood of regaining consciousness. While 496 this is both a philosophical and phenomenological query, the assumption is based 497 on the research of neural correlates of consciousness [54][55][56][57][58]. Numerous studies 498 have demonstrated significant differences in the power spectra of DoC patients 499 compared to healthy controls [59][60][61][62]. While a state of consciousness frequently 500 results in a power spectrum akin to that of a healthy individual, the opposite is 501 not always true, and other factors might also be important (e.g., integration and 502 segregation) [63]). ...
Disorders of consciousness (DoC) pose significant challenges in neurology. Conventional neuromodulation therapies for DoC have exhibited limited success, with varying effectiveness among patients. In this study, we introduce a computational approach for constructing personalized stimulus signals capable of inducing healthy-like neural activity patterns in DoC patients.
Leveraging a simplified brain model based on neural field theory, we fit this model to the power spectrum of a patient with DoC and derive a personalized stimulus time series to induce a healthy-like power spectrum. By applying this stimulus to brain regions typically targeted by stimulation therapies such as deep brain stimulation and repetitive transcranial magnetic stimulation, we demonstrate in silico, the ability of our method to elicit EEG power spectra resembling those of healthy individuals.
We speculate that in the course of a long-term treatment, when the brain produces healthy-like activity, it may trigger intrinsic plasticity mechanisms, potentially leading to sustained improvements in the patient's condition. While further clinical adjustments and validation are needed, this novel approach offers promise in tailoring brain stimulation therapies for DoC patients. Moreover, it presents potential extensions to other conditions that could also benefit from brain stimulation therapies.
... On the one hand, in patients with VS/UWS, TMS pulses elicit only localized event-related potentials (ERPs). On the other hand, more diffused activity can be elicited in patients with MCS and fully conscious healthy subjects [11][12][13]. ...
Brain imaging studies have recently provided some evidence in favor of covert cognitive processes that are ongoing in patients with disorders of consciousness (DoC) (e.g., a minimally conscious state and vegetative state/unresponsive wakefulness syndrome) when engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, considering that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. The results indicate that some form of motor resonance is spared in a subset of patients with DoC, with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether diagnosed with VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and the difference between the resonance with biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials, following the stimulation of the median nerve at the wrist (i.e., the temporal marker signaling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.
... Of note, data processing was carried out identically to [9,18,19,21]. [26,32] were used to compute the integral between +8 and +350ms post-stimulus and entered into group analysis. ...
Background:
Acute ischemia triggers a number of cellular mechanisms not only leading to excitotoxic cell death but also to enhanced neuroplasticity, facilitating neuronal reorganization and functional recovery.
Objective:
Identifying their critical distinction and transferring these cellular mechanisms to neurophysiological correlates adaptable to patients is crucial to promote recovery post-stroke. The combination of TMS and EEG constitute a promising readout of neuronal network activity in stroke patients.
Methods:
Using this technique, we investigated the development of local signal processing and global network alterations of 40 stroke patients with motor deficits alongside neural reorganization from the acute to the chronic phase.
Results:
We show that the TMS-EEG response reflects information about reorganization and signal alterations associated with persistent motor deficits throughout the entire post-stroke period. Early post-stroke in subgroup of patients with severe motor deficits, TMS applied to the lesioned motor cortex evoked a sleep-like slow wave response associated with a cortical off-period, a manifestion of cortical bistability, as well as a rapid disruption of the TMS-induced formation of causal network effects. Mechanistically, these phenomena were linked to lesions affecting ascending activating brainstem fibers. Of note, sleep-like slow waves invariably vanished in the chronic phase, but were highly indicative of a poor functional outcome.
Conclusion:
In summary, we suggest that transient effects of sleep-like waves and cortical bistability within ipsilesional M1 resulting in excessive inhibition may block functional reorganization leading to a less favorable functional outcome post-stroke, pointing to a new therapeutic target to improve recovery of function.
... In patients with VS/UWS, TMS pulses elicit only localized event-related potentials (ERPs). On the other hand, more diffused activity can be elicited in patients with MCS and fully conscious healthy subjects [11][12][13]. ...
... However, baseline-normalized corticospinal excitability during action observation (and the AO/pendulum ratio) significantly correlated with the N20 amplitude, a measure of temporal activation of the primary somatosensory cortex considered to be of prognostic relevance in DoC [28]. Because we did not carry out a patient follow-up involving measures of consciousness impairment, our results are 11 not conclusive on the prognostic value of corticospinal excitability modulation in DoC. However, recent results advocate in this direction [56]. ...
Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.
... Signals were re-referenced to the average reference, SVD and ICA were applied (mean ± SEM retained ICA components for t0 and t1: 16.5 ± 1.9; 16.5 ± 1.6, respectively; W=32.5, P=0.99) and power spectral density (PSD) estimates were computed across segments for each channel using the Welch's method (2-s Hanning windows, 50% overlap). For each patient, PSD was averaged across the same channels used for TMS-EEG analysis (four contralesional and four perilesional) and further averaged across bins pertaining to the classical EEG frequency ranges (Delta: 0.5-4 Hz, Theta: 4-8 Hz; Alpha: 8-12 Hz; Beta: 12-20 Hz; Low Gamma: 20-30 Hz; High Gamma: [30][31][32][33][34][35][36][37][38][39][40]. In order to assess the presence of perilesional effects on EEG power, for each frequency band, an asymmetry index was calculated as the ratio of perilesional and contralesional power values. ...
... On the other hand, the disruption of lateral excitatory connectivity may lead to disfacilitation [25,26] and to the prevalence of local inhibitory influences [27][28][29] in perilesional areas. Irrespective of the combination of factors leading to perilesional bistability, the occurrence of OFFperiods may add on top of the effect of structural lesions contributing to the disruption of functional network activity [11,13,30]. Here we confirm this effect by showing that the intrusion of sleep-like dynamics was associated with the disruption of local cortical interactions (Fig. 2). ...
... The key finding of this study, however, is that perilesional cortical bistability (Fig. 1) and the associated effects (Fig. 2) can be reversible. While cortical sleep-like dynamics and their network consequences are known to be reversible upon awakening from physiological sleep and several forms of general anesthesia [31][32][33][34], initial evidence in severely brain-injured patients suggests reversibility also in pathological conditions [11,30]. Substantiating such possibility, it is noteworthy that all the mechanisms involved in the generation of bistability after brain injury are known to undergo dynamic changes during stroke recovery. ...
Introduction
Recent studies have shown that, following brain injury, sleep-like cortical dynamics intrude into wakefulness, potentially contributing to brain network disruption and behavioral deficits.
Aim
We employ TMS in combination with EEG to detect these dynamics and assess their impact on brain networks and clinical evolution in awake stroke patients.
Methods
Twelve patients with subacute unilateral ischemic cortical stroke underwent a longitudinal study with two assessments (t0 and t1), including clinical evaluation using the National Institutes of Health Stroke Scale (NIHSS) and TMS-EEG recordings targeting perilesional and contralesional cortical sites. Parameters such as slow wave amplitude (SWa), high-frequency power (HFp) suppression, and the Perturbational Complexity Index-state transition (PCIst) were analyzed to quantify sleep-like cortical dynamics and their network-level consequences.
Results
Results demonstrated a significant clinical improvement (NIHSS score: 7.16±0.73 at t0, 4.33±0.74 at t1; W=78, P<0.001). Perilesional SWa and HFp suppression decreased significantly at t1 compared to t0 (T(11)=3.05, P=0.01 and T(11)=-3.39, P<0.01, respectively), along with recovery of PCIst values (T(11)=-2.35, P=0.04). Importantly, both the dissipation of sleep-like perilesional cortical dynamics and the recovery of network-level interactions correlated with patients’ clinical improvement (Spearman ρ=0.62, P=0.03; ρ=-0.68, P=0.01, respectively).
Conclusion
These findings underscore the potential of TMS-EEG as an objective measure of neurological evolution and suggest targeting sleep-like cortical dynamics as a viable strategy for post-stroke neuromodulation and rehabilitation.
... In patients with VS/UWS, TMS pulses elicit only localized event-related potentials (ERPs). On the other hand, more diffused activity can be elicited in patients with MCS and fully conscious healthy subjects [11][12][13]. ...
... However, baseline-normalized corticospinal excitability during action observation (and the AO/pendulum ratio) significantly correlated with the N20 amplitude, a measure of temporal activation of the primary somatosensory cortex considered to be of prognostic relevance in DoC [28]. Because we did not carry out a patient follow-up involving measures of consciousness impairment, our results are 11 not conclusive on the prognostic value of corticospinal excitability modulation in DoC. However, recent results advocate in this direction [56]. ...
Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.
... Electroencephalography (EEG) is commonly used in assessing brain activities in patients with brain diseases. Existing research has leveraged EEG to evaluate various aspects in patients with DOC, including the resting-state brain condition (13), event-related brain activities (14), sleeping (15), and neural responsiveness (16). Of these, resting-state EEG is particularly informative in monitoring and capturing the characteristics of patients' foundational neural activities (17). ...
Objective
Most brain function assessments for disorders of consciousness (DOC) utilized quantified characteristics, measured only once, ignoring the variation of patients' brain states. The study aims to investigate the brain activities of patients with DOC from a new perspective: variability of a large timescale functional network.
Methods
Forty-nine patients were enrolled in this study and performed a 1-week behavioral assessment. Subsequently, each patient received electroencephalography (EEG) recordings five times daily at 2-h intervals. Functional connectivity and networks were measured by weighted phase lag index and complex network parameters (characteristic path length, cluster coefficient, and betweenness centrality). The relative coefficient of variation (CV) of network parameters was measured to evaluate functional network variability.
Results
Functional networks of patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS) showed significantly higher segregation (characteristic path length) and lower centrality (betweenness centrality) than emerging from the minimal conscious state (EMCS) and minimal conscious state (MCS), as well as lower integration (cluster coefficient) than MCS. The functional networks of VS/UWS patients consistently presented the highest variability in segregation and integration (i.e., highest CV values of characteristic path length and cluster coefficient) on a larger time scale than MCS and EMCS. Moreover, the CV values of characteristic path length and cluster coefficient showed a significant inverse correlation with the Coma Recovery Scale-Revised scores (CRS-R). The CV values of network betweenness centrality, particularly of the cento-parietal region, showed a positive correlation with the CRS-R.
Conclusion
The functional networks of VS/UWS patients present the most invariant segregation and integration but divergent centrality on the large time scale networks than MCS and EMCS.
Significance
The variations observed within large timescale functional networks significantly correlate with the degree of consciousness impairment. This finding augments our understanding of the neurophysiological mechanisms underpinning disorders of consciousness.
... In terms of reference analysis, the earliest of the 10 most cited articles was published in 2012, while the latest was published in 2019, where, BRAIN (Rosanova et al., 2012) and, LANCET NEUROL (Thibaut et al., 2019) were defined as classic literature by the bibliometric method, highlighted their significant academic value in this field. Additionally, the most relevant citer to the largest cluster was "Assessing consciousness in coma and related states using transcranial magnetic stimulation combined with electroencephalography. " This review pointed out that TMS-EEG has great potential in identifying consciousness markers at the individual level, and may be of great value for clinicians in assessing consciousness . ...
... Additionally, the most relevant citer to the largest cluster was "Assessing consciousness in coma and related states using transcranial magnetic stimulation combined with electroencephalography. " This review pointed out that TMS-EEG has great potential in identifying consciousness markers at the individual level, and may be of great value for clinicians in assessing consciousness . Moreover, through examination of the three innovative studies, by Thibaut et al. (2014), Rosanova et al. (2012) and Ferrarelli et al. (2010), it was found that NINT, especially TMS and tDCS, played a significant role in the evaluation and management of DOC. NINT seems to have more advantages in treating disorders of consciousness, but the reasons are complex. ...
Background
The characteristics of disorders of consciousness (DOC) are changes in arousal and/or awareness caused by severe brain injuries. To date, the management of DOC patients remains a complex and challenging task, and neuromodulation techniques offer a promising solution. However, a bibliometric analysis focusing on neuromodulation techniques in DOC is currently absent. The aim of this study is to provide a bibliometric visualization analysis to investigate the research hotspots and frontiers in the field of neuromodulation techniques in DOC from 2012 to 2022.
Methods
The publications were collected and retrieved from the Web of Science (WoS) from 2012 to 2022. CiteSpace and Microsoft Excel were utilized perform the first global bibliographic analysis of the literature related to neuromodulation techniques for DOC.
Results
The analysis included a total of 338 publications. From 2012 to 2022, a consistent yet irregular increase in the number of articles published on neuromodulation techniques in DOC was observed. Frontiers in Neurology published the highest number of papers (n = 16). Neurosciences represented the main research hotspot category (n = 170). The most prolific country, institution, and author were the USA (n = 105), the University of Liege (n = 41), and Laureys Steven (n = 38), respectively. An analysis of keywords revealed that UWS/VS, MCS, and TMS constituted the primary research trends and focal points within this domain.
Conclusion
This bibliometric study sheds light on the current progress and emerging trends of neuromodulation techniques in DOC from 2012 to 2022. The focal topics in this domain encompass the precise diagnosis of consciousness levels in patients suffering from DOC and the pursuit of efficacious neuromodulation-based evaluation and treatment protocols for such patients.
... To capture the relationship between the resting-state EEG measures and the patient neurobehavioral condition assessed using CRS-R scale, we introduced two separate models: Model 1 with a total CRS-R score (labeled further as CRSscore) and Model 2 with a CRS-R based diagnosis (labeled further as CRSdiagnosis), as respective outcomes. We adopted the total CRS-R score (range 2-23 with the mean of 10.714 ± 5.941), as the index of the overall level of neurocognitive capacity in PDOC patients (Bodart et al. 2018;Rosanova et al. 2012). The CRS-R-based PDOC diagnosis was treated as an ordinal categorical variable. ...
... For this type, most of the signal energy is accumulated within delta range with a dominant profile 1/f in the spectrum. This spectral profile was observed mostly in the UWS group and can be interpreted as evidence for the low excitability of the cerebral cortex (Rosanova et al. 2012) and could be linked to the extensive functional and structural thalamocortical dysfunction. The dominance of delta-range activity has been previously reported in the studies of resting-state EEG in severe cases of brain lesions with UWS/VS diagnosis (eg. ...
The prolonged disorders of consciousness (PDOC) pose a challenge for an accurate clinical diagnosis, mainly due to patients’ scarce or ambiguous behavioral responsiveness. Measurement of brain activity can support better diagnosis, independent of motor restrictions. Methods based on spectral analysis of resting-state EEG appear as a promising path, revealing specific changes within the internal brain dynamics in PDOC patients. In this study we used a robust method of resting-state EEG power spectrum parameter extraction to identify distinct spectral properties for different types of PDOC. Sixty patients and 37 healthy volunteers participated in this study. Patient group consisted of 22 unresponsive wakefulness patients, 25 minimally conscious patients and 13 patients emerging from the minimally conscious state. Ten minutes of resting EEG was acquired during wakefulness and transformed into individual power spectra. For each patient, using the spectral decomposition algorithm, we extracted maximum peak frequency within 1–14 Hz range in the centro-parietal region, and the antero-posterior (AP) gradient of the maximal frequency peak. All patients were behaviorally diagnosed using coma recovery scale-revised (CRS-R). The maximal peak frequency in the 1–14 Hz range successfully predicted both neurobehavioral capacity of patients as indicated by CRS-R total score and PDOC diagnosis. Additionally, in patients in whom only one peak within the 1–14 Hz range was observed, the AP gradient significantly contributed to the accuracy of prediction. We have identified three distinct spectral profiles of patients, likely representing separate neurophysiological modes of thalamocortical functioning. Etiology did not have significant influence on the obtained results.
