GABAA Receptor Deficits Predict Recovery in Patients With Disorders of Consciousness: A Preliminary Multimodal [11C]Flumazenil PET and fMRI Study

Disorders of consciousness (DoC)—that is, unresponsive wakefulness syndrome/vegetative state and minimally conscious state—are debilitating conditions for which no reliable markers of consciousness recovery have yet been identified. Evidence points to the GABAergic system being altered in DoC, making it a potential target as such a marker

Spontaneous activity in default-mode network predicts ascriptions of self-relatedness to stimuli

Spontaneous activity levels prior to stimulus presentation can determine how that stimulus will be perceived. It has also been proposed that such spontaneous activity, particularly in the default-mode network (DMN), is involved in self-related processing. We therefore hypothesised that pre-stimulus activity levels in the DMN predict whether a stimulus is judged as self-related or not. Method: Participants were presented in the MRI scanner with a white noise stimulus that they were instructed contained their name or another. They then had to respond with which name they thought they heard. Regions where there was an activity level difference between self and other response trials two seconds prior to the stimulus being presented were identified. Results: Pre-stimulus activity levels were higher in the right temporoparietal junction (RTPJ), the right temporal pole (RTP), and the left superior temporal gyrus in trials where the participant responded that they heard their own name than trials where they responded that they heard another. Conclusion: Pre-stimulus spontaneous activity levels in particular brain regions, largely overlapping with the DMN, predict the subsequent judgement of stimuli as self-related. This extends our current knowledge of self-related processing and its apparent relationship with intrinsic brain activity in what can be termed a rest-self overlap

Disrupted neural variability during propofol‐induced sedation and unconsciousness

Variability quenching is a widespread neural phenomenon in which trial‐to‐trial variability (TTV) of neural activity is reduced by repeated presentations of a sensory stimulus. However, its neural mechanism and functional significance remain poorly understood. Recurrent network dynamics are suggested as a candidate mechanism of TTV, and they play a key role in consciousness. We thus asked whether the variability‐quenching phenomenon is related to the level of consciousness. We hypothesized that TTV reduction would be compromised during reduced level of consciousness by propofol anesthetics. We recorded functional magnetic resonance imaging signals of resting‐state and stimulus‐induced activities in three conditions: wakefulness, sedation, and unconsciousness (i.e., deep anesthesia). We measured the average (trial‐to‐trial mean, TTM) and variability (TTV) of auditory stimulus‐induced activity under the three conditions. We also examined another form of neural variability (temporal variability, TV), which quantifies the overall dynamic range of ongoing neural activity across time, during both the resting‐state and the task. We found that (a) TTM deceased gradually from wakefulness through sedation to anesthesia, (b) stimulus‐induced TTV reduction normally seen during wakefulness was abolished during both sedation and anesthesia, and (c) TV increased in the task state as compared to resting‐state during both wakefulness and sedation, but not anesthesia. Together, our results reveal distinct effects of propofol on the two forms of neural variability (TTV and TV). They imply that the anesthetic disrupts recurrent network dynamics, thus prevents the stabilization of cortical activity states. These findings shed new light on the temporal dynamics of neuronal variability and its alteration during anesthetic‐induced unconsciousness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146388/1/hbm24304_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146388/2/hbm24304.pd

Why and how is the self related to the brain midline regions?

What the self is and where it comes from has been one of the great problems of philosophy for thousands of years. As science and medicine have progressed this question has moved to also become a central one in psychology, psychiatry, and neuroscience. The advent of in vivo brain imaging has now allowed the scientific investigation of the self to progress further than ever. Many such imaging studies have indicated that brain structures along the cortical midline are particularly closely related to self-specific processing. This association between cortical midline structures (CMS) and self is reinforced by the involvement of these regions in other self-oriented processes, such as mind-wandering or stimulus valuation. Those midline regions involved in self- processing also overlap with another network, the default mode network, which shows high brain activity during the so-called resting state, indicating that there may be a special relationship between self-processing and intrinsic activity. Although such promising groundwork linking the self and CMS has been carried out, many questions remain. These include: what features of the midline regions lead to their apparent importance in self-processing? How can we appropriately account for confounding factors such as familiarity or task-effects in our experiments? How is the self-related to other features of the mind, such as consciousness? How is our methodology influencing our attempts to link the self and the brain? The purpose of this ebook is to address some of these questions, including opinions, perspectives, and hypotheses about the concept of the self, the relationship between CMS and the self, and the specific function of these brain regions in self-processing. It also includes original research papers describing EEG, fMRI, and behavioral experiments investigating different aspects of the self

Distinct Effects of Stimulus Repetition on Various Temporal Stages of Subject’s Own Name Processing

The self is one of the most important concepts in psychology, which is of great significance for human survival and development. As an important self-related stimulus, the subject’s own name (SON) shows great advantages in cognitive and social processing and is widely used as an oddball stimulus in previous studies. However, it remained unknown whether the multiple repetition of stimulus would have similar influence on the neural response to SON and the other names under equal probability. In this study, adopting EEG and an equal–probability paradigm, we first detected the SON-related ERP components which could differentiate SON from other names, and then investigated how these components are influenced by repeated exposure of the stimulus. Our results showed that SON evoked an earlier SON-related negativity (SRN) at the fronto-central region and a late positive potential (LPP) at the centro-parietal region. More intriguingly, the earlier SRN demonstrated reduction after multiple repetitions, whereas LPP did not exhibit significant changes. In conclusion, these findings revealed that multiple repetitions of the stimulus might influence the various temporal stages in SON-related processing and highlighted the robustness of the late stage in this processing

Dual interaction between heartbeat-evoked responses and stimuli

Heartbeat-evoked responses (HERs) can interact with external stimuli and play a crucial role in shaping perception, self-related processes, and emotional processes. On the one hand, the external stimulus could modulate HERs. On the other hand, the HERs could affect cognitive processing of the external stimulus. Whether the same neural mechanism underlies these two processes, however, remains unclear. Here, we investigated this interactive mechanism by measuring HERs using magnetoencephalography (MEG) and two name perception tasks. Specifically, we tested (1) how hearing a subject's own name (SON) modulates HERs and (2) how the judgment of an SON is biased by prestimulus HERs. The results showed a dual interaction between HERs and SON. In particular, SON can modulate HERs for heartbeats occurring from 200 to 1200 ms after SON presentation. In addition, prestimulus HERs can bias the SON judgment when a stimulus is presented. Importantly, MEG activities from these two types of interactions differed in spatial and temporal patterns, suggesting that they may be associated with distinct neural pathways. These findings extend our understanding of brain-heart interactions

Localizing Spectral Interactions in the Resting State Network Using the Hilbert–Huang Transform

Brain synchronizations are orchestrated from neuronal oscillations through frequency interactions, such as the alpha rhythm during relaxation. Nevertheless, how the intrinsic interaction forges functional integrity across brain segregations remains elusive, thereby motivating recent studies to localize frequency interactions of resting-state fMRI (rs-fMRI). To this point, we aim to unveil the fMRI-based spectral interactions using the time-frequency (TF) analysis; however, Fourier-based TF analyses impose restrictions on revealing frequency interactions given the limited time points in fMRI signals. Instead of using the Fourier-based wavelet analysis to identify the fMRI frequency of interests, we employed the Hilbert–Huang transform (HHT) for probing the specific frequency contribution to the functional integration, called ensemble spectral interaction (ESI). By simulating data with time-variant frequency changes, we demonstrated the Hilbert TF maps with high spectro-temporal resolution and full accessibility in comparison with the wavelet TF maps. By detecting amplitude-to-amplitude frequency couplings (AAC) across brain regions, we elucidated the ESI disparity between the eye-closed (EC) and eye-open (EO) conditions in rs-fMRI. In the visual network, the strength of the spectral interaction within 0.03–0.04 Hz was amplified in EC compared with that in EO condition, whereas a canonical connectivity analysis did not present differences between conditions. Collectively, leveraging from the instantaneous frequency of HHT, we firstly addressed the ESI technique to map the fMRI-based functional connectivity in a brand-new AAC perspective. The ESI possesses potential in elucidating the functional connectivity at specific frequency bins, thereby providing additional diagnostic merits for future clinical neuroscience

Mismatch negativity to the patient's own name in chronic disorders of consciousness

Previous studies implicated potential value of mismatch negativity (MMN) in predicting recovery of consciousness in patients with disorders of consciousness (DOC). We have adopted a novel MMN evoked by subject's own name (SON), a self-referential stimulus thought to be powerful in evoking residual brain activity, and examined the correlation between the MMN and recovery of consciousness in patients with chronic (> 1 month) DOC. Twelve patients and 12 age-matched healthy controls were investigated. The patients were diagnosed as coma (n = 4). vegetative state (VS, n = 6), and minimally conscious state (MCS, n = 2), mainly based on the JFK Coma Recovery Scale-Revised. The SON-evoked MMN (SON-MMN) was present in seven patients. Critically, the presence of SON-MMN was significantly correlated with recovery of consciousness. While four of the five patients (three VS and two coma) showing SON-MMN changed to MCS 3 months later, the rest of the patients (three VS and two coma) without SON-MMN failed to show any clinical improvement. Our study thus illustrates that the subject's own name is effective in evoking MMN in patients with DOC, and that SON-MMN has potential prognostic values in predicting recovery of consciousness.Previous studies implicated potential value of mismatch negativity (MMN) in predicting recovery of consciousness in patients with disorders of consciousness (DOC). We have adopted a novel MMN evoked by subject's own name (SON), a self-referential stimulus thought to be powerful in evoking residual brain activity, and examined the correlation between the MMN and recovery of consciousness in patients with chronic (> 1 month) DOC. Twelve patients and 12 age-matched healthy controls were investigated. The patients were diagnosed as coma (n = 4). vegetative state (VS, n = 6), and minimally conscious state (MCS, n = 2), mainly based on the JFK Coma Recovery Scale-Revised. The SON-evoked MMN (SON-MMN) was present in seven patients. Critically, the presence of SON-MMN was significantly correlated with recovery of consciousness. While four of the five patients (three VS and two coma) showing SON-MMN changed to MCS 3 months later, the rest of the patients (three VS and two coma) without SON-MMN failed to show any clinical improvement. Our study thus illustrates that the subject's own name is effective in evoking MMN in patients with DOC, and that SON-MMN has potential prognostic values in predicting recovery of consciousness. (c) 2008 Elsevier Ireland Ltd. All rights reserved

Eyes-Open and Eyes-Closed Resting State Network Connectivity Differences

Resting state networks comprise several brain regions that exhibit complex patterns of interaction. Switching from eyes closed (EC) to eyes open (EO) during the resting state modifies these patterns of connectivity, but precisely how these change remains unclear. Here we use functional magnetic resonance imaging to scan healthy participants in two resting conditions (viz., EC and EO). Seven resting state networks were chosen for this study: salience network (SN), default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), visual network (VN), motor network (MN) and auditory network (AN). We performed functional connectivity (FC) analysis for each network, comparing the FC maps for both EC and EO. Our results show increased connectivity between most networks during EC relative to EO, thereby suggesting enhanced integration during EC and greater modularity or specialization during EO. Among these networks, SN is distinctive: during the transition from EO to EC it evinces increased connectivity with DMN and decreased connectivity with VN. This change might imply that SN functions in a manner analogous to a circuit switch, modulating resting state relations with DMN and VN, when transitioning between EO and EC

Dissociation Between Anterior and Posterior Cortical Regions During Self-Specificity and Familiarity: A Combined fMRI–Meta-Analytic Study

The familiarity to the subject of any potential stimuli presents one of the major difficulties for the investigation of the self; the separation of effects resulting from familiarity from self-effects being extremely problematic. The aim of this study was thus to investigate the neural distinction between self and familiarity by combining two sets of fMRI data with a meta-analysis. In the first fMRI experiment, regions responding to self/ familiarity were investigated using the subject’s own name and names of familiar others. These effects were confirmed and extended in a second fMRI experiment using the subject’s own name and a stranger’s name, as spoken by familiar and unfamiliar voices. Finally, a meta-analysis of self- and familiarity-related studies was conducted. Neural activity in the anterior brain regions, such as the anterior cingulate (ACC) and anterior insula (AI), was found to be specific for self-specific stimuli. In contrast, posterior brain regions, such as the posterior cingulate, were activated by familiar stimuli. Finally, the distinction between anterior and posterior regions for self and familiarity was confirmed by meta-analytic data. This study demonstrates a clear anterior–posterior cortical partition between self-specificity and familiarity