Causal Connectivity According to Conscious Experience in Non-Rapid Eye Movement Sleep

What is the central question of this study? A transcranial magnetic stimulation (TMS)-induced twitch applied on isolated single breaths over the motor cortex somatotopic representation of the tongue briefly recruits submental muscles and improves airflow dynamics of flow-limited respiratory cycles without arousing sleep apnoea patients. However, the mechanical impact of the TMS-induced twitch applied during consecutive breathing cycles on airflow dynamics remains unknown. What is the main finding and what is its importance? Our results show that application of TMS with the stimulator output set at the sleep submental motor threshold intensity on consecutive respiratory cycles increases inspiratory flow and reduces the turbulent airflow component. These results indicate an improvement of airflow pattern after two single consecutive TMS-induced twitches without arousing sleep apnoea patients. Transcranial magnetic stimulation (TMS)-induced twitches applied on isolated breaths briefly recruit upper airway dilator muscles and improve airflow and inspiratory volume without arousing apnoeic patients from sleep, but the effects of applying such twitches consecutively on airflow dynamics is unknown. The objective of this study was to quantify the effects of five consecutive TMS-induced twitches applied on sleep-induced obstructive hypopnoeic breaths in 10 obstructive sleep apnoea patients. Submental muscle motor threshold (SUBMT) and motor-evoked potential were measured during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, at the beginning of inspiration of consecutive flow-limited respiratory cycles, with the stimulator output set at sleep SUBMT. Maximal inspiratory flow, inspiratory volume, inspiratory time, shifts of electroencephalogram frequency and pulse rate variability were assessed. During sleep, SUBMT increased (wakefulness, 25.3 ± 4.9%; NREM sleep, 27.0 ± 6.2%; P = 0.02). During each series of stimulations there was a rise in maximal inspiratory flow (from 306.7 ± 123.2 to 359.8 ± 154.1 ml s(-1); P = 0.0002) and in inspiratory volume (from 346.1 ± 128.1 to 414.9 ± 171.2 ml; P = 0.02) without differences in thoraco-abdominal efforts and inspiratory time. These responses were observed in the absence of arousals and ceased immediately after TMS interruption. Transcranial magnetic stimulation-induced cortical and/or autonomic arousal was observed in 30.2% of all series of stimulation. Consecutive twitch TMS of submental muscles may lead to arousals in a minority of patients but can be applied on consecutive respiratory cycles during sleep and can significantly improve maximal inspiratory flow and inspiratory volume of flow-limited cycles.

The neuronal connectivity patterns that differentiate consciousness from unconsciousness remain unclear. Previous studies have demonstrated that effective connectivity, as assessed by transcranial magnetic stimulation combined with electroencephalography (TMS–EEG), breaks down during the loss of consciousness. This study investigated changes in EEG connectivity associated with consciousness during non-rapid eye movement (NREM) sleep following parietal TMS. Compared with unconsciousness, conscious experiences during NREM sleep were associated with reduced phase-locking at low frequencies (<4 Hz). Transitivity and clustering coefficient in the delta and theta bands were also significantly lower during consciousness compared to unconsciousness, with differences in the clustering coefficient observed in scalp electrodes over parietal–occipital regions. There were no significant differences in Granger-causality patterns in frontal-to-parietal or parietal-to-frontal connectivity between reported unconsciousness and reported consciousness. Together these results suggest that alterations in spectral and spatial characteristics of network properties in posterior brain areas, in particular decreased local (segregated) connectivity at low frequencies, is a potential indicator of consciousness during sleep.

The aim of the study was to investigate differences in cortical networks based on the state of consciousness. Five subjects performed a serial-awakening paradigm with electroencephalography (EEG) recordings. We considered four states of consciousness: (1) non-rapid eye movement (NREM) sleep with no conscious experience, (2) NREM sleep with conscious experience, (3) rapid eye movement (REM) sleep with conscious experience, and (4) wakefulness. We applied graph theoretical analysis to explore the cortical connectivity and network properties in five frequency bands. Connectivity between EEG channels was evaluated with the weighted phase lag index (wPLI). The characteristic path length, transitivity, and clustering coefficient were computed to evaluate functional integration and segregation of the associated brain network. There were no significant differences in wPLI among the four states of consciousness. In the beta band, functional integration in wakefulness was higher than in NREM sleep. Regarding functional segregation, in the theta band, transitivity and clustering coefficient in NREM sleep with no conscious experience were stronger than in wakefulness or REM sleep, but clustering in the beta band showed an opposite effect. The observed differences may be related to cortical bistability and add to previously observed neural correlates of consciousness.

Tactile extinction has been interpreted as an attentional disorder, closely related to hemineglect, due to hyperactivation of the unaffected hemisphere, resulting in an ipsilesional attentional bias. Paired transcranial magnetic stimulation (TMS) techniques, with a subthreshold conditioning stimulus (CS) followed at various interstimulus intervals (ISIs) by a suprathreshold test stimulus (TS), are useful for investigating intracortical inhibition and facilitation in the human motor cortex. In the present work, we investigated the effects of paired TMS over the posterior parietal and frontal cortex of the unaffected hemisphere in a group of eight right-brain-damaged patients with tactile extinction who were carrying out a bimanual tactile discrimination task. The aim of the study was to verify if paired TMS could induce selective inhibition or facilitation of the unaffected hemisphere depending on the ISI, resulting, respectively, in an improvement and a worsening of contralesional extinction. In addition, we wanted to investigate if the effects of parietal and frontal TMS on contralesional extinction appeared at different intervals, suggesting time-dependent activation in the cortical network for the processing of tactile spatial information. Paired TMS stimuli with a CS and a TS, separated by two ISIs of 1 and 10 ms, were applied over the left parietal and frontal cortex after various intervals from the presentation of bimanual cutaneous stimuli. Single-test parietal TMS stimuli improved the patients' performance, whereas paired TMS had distinct effects depending on the ISI: at ISI = 1 ms the improvement in extinction was greater than that induced by single-pulse TMS; at ISI = 10 ms we observed worsening of extinction, with complete reversal of the effects of single-pulse TMS. Compared with TMS delivered over the frontal cortex, parietal TMS improved the extinction rate in a time window that began earlier. These findings shed further light on the mechanism of tactile extinction, suggesting relative hyperexcitability of the parieto-frontal network in the unaffected hemisphere, which is amenable to study and modulation by paired TMS pulses. In addition, the results show time-dependent processing of tactile spatial information in the parietal and frontal cortices, with a bimodal distribution of activity, at least in the attentional network of the unaffected hemisphere.

Sleep and anesthesia entail alterations in conscious experience. Conscious experience may be absent (unconsciousness) or take the form of dreaming, a state in which sensory stimuli are not incorporated into conscious experience (disconnected consciousness). Recent work has identified features of cortical activity that distinguish conscious from unconscious states; however, less is known about how cortical activity differs between disconnected states and normal wakefulness. We employed transcranial magnetic stimulation–electroencephalography (TMS–EEG) over parietal regions across states of anesthesia and sleep to assess whether evoked oscillatory activity differed in disconnected states. We hypothesized that alpha activity, which may regulate perception of sensory stimuli, is altered in the disconnected states of rapid eye movement (REM) sleep and ketamine anesthesia. Compared to wakefulness, evoked alpha power (8–12 Hz) was decreased during disconnected consciousness. In contrast, in unconscious states of propofol anesthesia and non-REM (NREM) sleep, evoked low-gamma power (30–40 Hz) was decreased compared to wakefulness or states of disconnected consciousness. These findings were confirmed in subjects in which dream reports were obtained following serial awakenings from NREM sleep. By examining signatures of evoked cortical activity across conscious states, we identified novel evidence that suppression of evoked alpha activity may represent a promising marker of sensory disconnection.

GENERAL COMMENTARY article Front. Hum. Neurosci., 20 December 2013Sec. Cognitive Neuroscience Volume 7 - 2013 | https://doi.org/10.3389/fnhum.2013.00891

Transcranial magnetic stimulation (TMS) can activate the corticobulbar system and briefly recruit upper airway dilator muscles, improving the inspiratory airflow dynamics of flow-limited respiratory cycles during sleep. The purpose of this investigation was to quantify the effects of TMS-induced twitches applied during sleep on flow-limited respiratory cycles in 14 obstructive sleep apnoea patients. Submental muscle motor threshold (SUB(MT)) and motor-evoked potential (SUB(MEP)) were examined during wakefulness and sleep. The TMS-induced twitches were applied during stable non-rapid eye movement (NREM) sleep, during non-consecutive flow-limited respiratory cycles at the beginning of inspiration, with intensities varying from sleep SUB(MT) up to maximal stimulation without arousal. Maximal inspiratory flow, inspiratory volume, shifts of electroencephalogram frequency and pulse rate variability were assessed. Cortical and/or autonomic arousal after TMS was observed in only 13.8% of all twitches applied. The SUB(MT) increased during NREM sleep (wakefulness, 24.8 ± 9.3%; and NREM sleep, 28.3 ± 9.5%; P = 0.003). Augmenting stimulator output from SUB(MT) to maximal stimulation before arousal enhanced SUB(MEP) peak-to-peak amplitude (from 0.09 ± 0.05 to 0.4 ± 0.3 mV; P = 0.005) with a concomitant rise in maximal inspiratory flow (from 376.2 ± 107.9 to 411.9 ± 109.3 ml s(-1); P = 0.008) and inspiratory volume (from 594.8 ± 189.2 to 663.7 ± 203.1 ml; P = 0.001) in all but one patient. Corticobulbar excitability of submental muscles decreases during NREM sleep. Brief recruitment of submental muscles with TMS during sleep improves upper airway mechanics without arousing patients from sleep.

AimThe objective of this work was to demonstrate the usefulness of a novel statistical method to study the impact of transcranial magnetic stimulation (TMS) on brain connectivity in patients with depression using different stimulation protocols, i.e., 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3).MethodsElectroencephalography (EEG) connectivity analysis was performed using Directed Transfer Function (DTF) and a set of 21 indices based on graph theory. The statistical analysis of graph-theoretic indices consisted of a combination of the k-NN rule, the leave-one-out method, and a statistical test using a 2 × 2 contingency table.ResultsOur new statistical approach allowed for selection of the best set of graph-based indices derived from DTF, and for differentiation between conditions (i.e., before and after TMS) and between TMS protocols. The effects of TMS was found to differ based on frequency band.ConclusionA set of four brain asymmetry measures were particularly useful to study protocol- and frequency-dependent effects of TMS on brain connectivity.SignificanceThe new approach would allow for better evaluation of the therapeutic effects of TMS and choice of the most appropriate stimulation protocol.

Simple SummaryDuring the deep phases of sleep we do not normally wake up by a thunder, but we nevertheless notice it when awake. The exact same sound gets to our ears and cortex through the thalamus and still, it triggers two very different responses. There is growing experimental evidence that these two states of the brain—sleep and wakefulness—distribute sensory information in different ways across the cortex. In particular, during sleep, neuronal responses remain local and do not spread out across distant synaptically connected regions. On the contrary, during wakefulness, stimuli are able to elicit a wider spatial response. We have used a computational model of coupled cortical columns to study how these two propagation modes arise. Moreover, the transition from sleep-like to waking-like dynamics occurs in agreement with the synaptic homeostasis hypothesis and only requires the increase of excitatory conductances. We have found that, in order to reproduce the aforementioned observations, this parameter change has to be selectively applied: synaptic conductances between distinct columns have to be potentiated over local ones.Non-threatening familiar sounds can go unnoticed during sleep despite the fact that they enter our brain by exciting the auditory nerves. Extracellular cortical recordings in the primary auditory cortex of rodents show that an increase in firing rate in response to pure tones during deep phases of sleep is comparable to those evoked during wakefulness. This result challenges the hypothesis that during sleep cortical responses are weakened through thalamic gating. An alternative explanation comes from the observation that the spatiotemporal spread of the evoked activity by transcranial magnetic stimulation in humans is reduced during non-rapid eye movement (NREM) sleep as compared to the wider propagation to other cortical regions during wakefulness. Thus, cortical responses during NREM sleep remain local and the stimulus only reaches nearby neuronal populations. We aim at understanding how this behavior emerges in the brain as it spontaneously shifts between NREM sleep and wakefulness. To do so, we have used a computational neural-mass model to reproduce the dynamics of the sensory auditory cortex and corresponding local field potentials in these two brain states. Following the synaptic homeostasis hypothesis, an increase in a single parameter, namely the excitatory conductance , allows us to place the model from NREM sleep into wakefulness. In agreement with the experimental results, the endogenous dynamics during NREM sleep produces a comparable, even higher, response to excitatory inputs to the ones during wakefulness. We have extended the model to two bidirectionally connected cortical columns and have quantified the propagation of an excitatory input as a function of their coupling. We have found that the general increase in all conductances of the cortical excitatory synapses that drive the system from NREM sleep to wakefulness does not boost the effective connectivity between cortical columns. Instead, it is the inter-/intra-conductance ratio of cortical excitatory synapses that should raise to facilitate information propagation across the brain.

Transcranial magnetic stimulation (TMS) has been used to document some apparent interhemispheric influences behaviorally, with TMS over the right parietal cortex reported to enhance processing of touch for the ipsilateral right hand (Seyal et al., 1995). However, the neural bases of such apparent interhemispheric influences from TMS remain unknown. Here, we studied this directly by combining TMS with concurrent functional magnetic resonance imaging (fMRI). We applied bursts of 10 Hz TMS over right parietal cortex, at a high or low intensity, during two sensory contexts: either without any other stimulation, or while participants received median nerve stimulation to the right wrist, which projects to left primary somatosensory cortex (SI). TMS to right parietal cortex affected the blood oxygenation level-dependent signal in left SI, with high- versus low-intensity TMS increasing the left SI signal during right-wrist somatosensory input, but decreasing this in the absence of somatosensory input. This state-dependent modulation of SI by parietal TMS over the other hemisphere was accompanied by a related pattern of TMS-induced influences in the thalamus, as revealed by region-of-interest analyses. A behavioral experiment confirmed that the same right parietal TMS protocol of 10 Hz bursts led to enhanced detection of perithreshold electrical stimulation of the right median nerve, which is initially processed in left SI. Our results confirm directly that TMS over right parietal cortex can affect processing in left SI of the other hemisphere, with rivalrous effects (possibly transcallosal) arising in the absence of somatosensory input, but facilitatory effects (possibly involving thalamic circuitry) in the presence of driving somatosensory input.

Interplay between the cerebral hemispheres is vital for coordinating perception and behavior. One influential account holds that the hemispheres engage in rivalry, each inhibiting the other. In the somatosensory domain, a seminal paper claimed to demonstrate such interhemispheric rivalry, reporting improved tactile detection sensitivity on the right hand after transcranial magnetic stimulation (TMS) to the right parietal lobe (Seyal, Ro, & Rafal, 1995). Such improvement in tactile detection ipsilateral to TMS could follow from interhemispheric rivalry, if one assumes that TMS disrupted cortical processing under the coil and thereby released the other hemisphere from inhibition. Here we extended the study by Seyal et al. (1995) to determine the effects of right parietal TMS on tactile processing for either hand, rather than only the ipsilateral hand. We performed two experiments applying TMS in the context of median-nerve stimulation; one experiment required somatosensory detection, the second somatosensory intensity discrimination. We found different TMS effects on detection versus discrimination, but neither set of results followed the prediction from hemispheric rivalry that enhanced performance for one hand should invariably be associated with impaired performance for the other hand, and vice-versa. Our results argue against a strict rivalry interpretation, instead suggesting that parietal TMS can provide a pedestal-like increment in somatosensory response.

Can One Suppress Subliminal Words?

Effect of repetitive transcranial magnetic stimulation on fronto-posterior and hemispheric asymmetry in depression

Sleep is phenomenologically rich, teeming with different kinds of conscious thought and experience. Dreaming is the most prominent example, but there is more to conscious experience in sleep than dreaming. Especially in non‐rapid eye movement sleep, conscious experience, sometimes dreamful, sometimes dreamless, also alternates with a loss of consciousness. Yet while dreaming has become established as a topic for interdisciplinary consciousness science and empirically informed philosophy of mind, the same is not true of other kinds of sleep‐related experience, nor is it true of sleep itself. I argue that this is a mistake. Conscious experience in sleep is more diverse than dreaming and we need to explain its different forms as well as the alternation between conscious and unconscious sleep states. We also need to ask how different kinds of sleep‐related experience relate to foundational issues about sleep and wakefulness as well as sleep stages. I survey recent findings and theoretical developments from sleep and dream research to show how the traditional view of sleep and its relation to wakefulness and consciousness is flawed. I then suggest that by refining our frameworks of sleep‐related experiences and sleep staging in tandem, we can work toward a better view. As we are only beginning to understand the diversity of consciousness in sleep, an important aim is programmatic: We need a philosophy of sleep and of consciousness in sleep, not just a philosophy of dreaming, and a future theory of sleep needs to integrate phenomenological considerations with neuroscientific and behavioral evidence. Working toward such a theory will radically transform our understanding of sleep, wakefulness, and our conscious minds.

Frontal and parietal transcranial magnetic stimulation (TMS) disturbs programming of saccadic eye movements