Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt (...) bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements. -/- . (shrink)

Inducing the rubber hand illusion (RHI) requires that participants look at an imitation hand while it is stroked in synchrony with their occluded biological hand. Previous explanations of the RHI have emphasized multisensory integration, and excluded higher cognitive functions. We investigated the relationship between the RHI and higher cognitive functions by experimentally testing task switch (as measured by switch cost) and mind wandering (as measured by SART score); we also included a questionnaire for attentional control that comprises two subscales, attention-shift (...) and attention-focus. To assess experience of RHI, the Botvinick and Cohen (1998) questionnaire was used and illusion onset time was recorded. Our results indicate that rapidity of onset reliably indicates illusion strength. Regression analysis revealed that participants evincing less switch cost and higher attention-shift scores had faster RHI onset times, and that those with higher attention-shift scores experienced the RHI more vividly. These results suggest that the multi-sensory hypothesis is not sufficient to explain the illusion: higher cognitive functions should be taken into account when explaining variation in the experience of ownership for the rubber hand. (shrink)

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and (...) [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. (shrink)

Neurovascular coupling (NVC), the transient regional hyperemia following the evoked neuronal responses, is the basis of blood oxygenation level-dependent techniques and is generally adopted across physiological conditions, including the intrinsic resting state. However, the possibility of neurovascular dissociations across physiological alterations is indicated in the literature. To examine the NVC stability across sleep–wake states, we used electroencephalography (EEG) as the index of neural activity and functional magnetic resonance imaging (fMRI) as the measure of cerebrovascular response. Eight healthy adults were recruited (...) for simultaneous EEG-fMRI recordings in nocturnal sleep. We compared the cross-modality (EEG vs. fMRI) consistency of functional indices (spectral amplitude and functional connectivity) among five states of wakefulness and sleep (state effect). We also segregated the brain into three main partitions (anterior, middle and posterior) for spatial assessments (regional effect). Significant state effects were found on δ, α and fMRI indices and regional effects on the α and fMRI indices. However, the cross-state EEG changes in spectral amplitude and functional connectivity did not consistently match the changes in the fMRI indices across sleep–wake states. In spectral amplitude, the δ band peaked at the N3 stage for all brain regions, while the fMRI fluctuation amplitude peaked at the N2 stage in the central and posterior regions. In regional connectivity, the inter-hemispheric connectivity of the δ band peaked at the N3 stage for all regions, but the bilateral fMRI connectivity showed the state changes in the anterior and central regions. The cross-modality inconsistencies across sleep–wake states provided preliminary evidence that the neurovascular relationship may not change in a linear consistency during NREM sleep. Thus, caution shall be exercised when applying the NVC presumption to investigating sleep/wake transitions, even among healthy young adults. (shrink)

Objective Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. -/- Method In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD (...) patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. -/- Results (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. -/- Conclusions These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations. (shrink)

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy controls (n (...) = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls. (shrink)

Background: Rumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging because of the need to distinguish self effects from the emotional content of task stimuli. This study employed an emotionally neutral self-related paradigm to investigate possible altered self-processing in depression and its link to rumination. Methods: People with major depressive disorder (n = 25) and controls (n = 25) underwent task-based electro-encephalogram recording. We studied late (...) event-related potentials, along with low-frequency oscillatory power. We compared electroencephalogram metrics between groups and correlated them with depressive symptoms and reported rumination. Results: Participants with major depressive disorder displayed a difference in late positive potentials across frontocentral electrodes between self-related and non-self-related conditions. We found no such difference in controls. The magnitude of this difference was positively correlated with depressive symptoms and reported rumination. Participants with major depressive disorder also had elevated theta oscillation power at central electrodes in self-related conditions, a finding that we did not see in controls. Limitations: Patients with major depressive disorder were medicated at the time of the study. The group studied was primarily female, so the observed effects may have been sex-specific. Conclusion: Rumination appears to be linked to altered self-related processing in depression, independent of stimuli-related emotional confounds. This connection between self-related processing and depression may point to a self disorder as a core component of depression. (shrink)

意識是如此不可捉摸又抽象的概念，「測量」意識簡直就像科幻小說情節。科學家近年來在這方面已大有進展，藉由各項腦造影技術和實驗手法，能夠分析不同意識狀態下的大腦活動型態。.

Objective: To evaluate the potential of arterial spin labeling (ASL) as an alternative to FDG-PET in the diagnosis of disorders of consciousness (DOC), we conducted a comparative study of the two modalities. Methods: A total of 36 DOC patients (11 female; mean age = 49.67 ± 14.54 years) and 17 healthy control (HC) participants (9 female; mean age = 31.9 ± 9.6 years) underwent both FDG-PET scans that measure metabolism via glucose uptake and ASL scans that measure cerebral blood flow (...) (CBF). CBF and metabolism in DOC and HC were compared, globally and for seven functional networks. Comparability of the two modalities was estimated using Spearman partial correlation for both global and network levels. Furthermore, a support vector machine (SVM) algorithm was used to train two classifiers to distinguish DOC patients from HC with normalized CBF or metabolism values from the seven networks. Performance of these classifiers was first evaluated through leave-one-subject-out (LOSO) cross-validation within their respective modalities. Subsequently, cross-modal validation was conducted: testing the ASL-trained classifier with PET data (ASL-to-PET validation) and vice versa (PET-to-ASL validation). Performance of each classifier was assessed using receiver operating characteristic (ROC) analysis, with area under the curve (AUC) as the metric. Results: Both modalities showed agreement in decreased CBF and metabolism in DOC patients compared to HC, at both global and network levels. The global brain and most networks showed significant positive partial correlation between CBF and metabolism. SVM classifiers, utilizing activity from seven networks as features, performed well in the both LOSO cross-validation (ASL-trained classifier: accuracy = 83.02%, AUC = 0.95; PET-trained classifier: accuracy = 98.12%, AUC = 0.98) and cross-modal validation (ASL-to-PET validation: accuracy = 84.90%, AUC =0.92; PET-to-ASL validation: accuracy = 73.58%, AUC = 0.93). Conclusion: Our results demonstrate that ASL provides information comparable to FDG-PET for DOC patients; moreover, classifiers trained on ASL data perform comparably well to those trained on FDG-PET data. Therefore, ASL could be a valuable alternative to FDG-PET in the clinical diagnosis of DOC, especially in light of its advantages: ease of acquisition, avoidance of radiation exposure, brevity of scanning time, and lower-cost. (shrink)

Even when brain scans fail to detect a striate lesion, functional evidence for blindsight can be adduced. In the aftermath of an automobile accident, JK became blind. Results of ophthalmic exams indicated that the blindness must be cortical. Nevertheless, multiple MRI scans failed to detect structural damage to the striate cortex. Prior to the accident JK had been an athlete; after the accident he retained some athletic abilities, arousing suspicions that he might be engaged in fraud. His residual athletic abilities—e.g., (...) hitting a handball or baseball, or catching a Frisbee—coupled with his experienced blindness, suggested blindsight. But due to the apparent absence of striate lesions, we designed a series of tasks for temporal and spatial dimensions in an attempt to detect functional evidence of his disability. Indeed, test results revealed compelling neural evidence that comport with his subjective reports. This spatiotemporal task-related method that includes contrasts with healthy controls, and detailed understanding of the patient's conscious experience, can be generalized for clinical, scientific and forensic investigations of blindsight. -/- . (shrink)

Invited Commentary On: Graziano, M. S. A., Guterstam, A., Bio, B. J., Wilterson, A. I. (2019). Toward a standard model of consciousness: Reconciling the attention schema, global workspace, higher order thought, and illusionist theories. Cognitive Neuropsychology.

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. (shrink)

Subjective perception of sleep is not necessarily consistent with electroencephalography (EEG) indications of sleep. The mismatch between subjective reports and objective measures is often referred to as “sleep state misperception.” Previous studies evince that this mismatch is found in both patients with insomnia and in normal sleepers, but the neurophysiological mechanism remains unclear. The aim of the study is to explore the neurophysiological basis of this mechanism, from the perspective of both EEG power and functional magnetic resonance imaging (fMRI) fluctuations. (...) Thirty-six healthy young adults participated in the study. Simultaneous EEG and fMRI recordings were conducted while the participants were trying to fall asleep in an MRI scanner at approximately 9:00 pm. They were awakened after achieving stable N1 or N2 sleep, or after 90 min without falling into stable sleep. Next they were asked to recall their conscious experiences from the moment immediately prior to awakening. Sixty-one instances of scheduled awakenings were collected: 21 of these after having achieved stable stage N2 sleep; 12, during stage N1 sleep; and, 20 during the waking state. Relative to those awakenings without subjective–objective discrepancy (n = 27), these awakenings with discrepancy (n = 14) were associated with lower θ power, as well as higher α, β, and γ power. Moreover, we found that participants who exhibited the discrepancy, compared with those who did not, evinced a higher amplitude of low-frequency fluctuation levels in the prefrontal cortex. These results lend support to the conjecture that the subjective–objective discrepancy is associated with central nervous system hyperarousal. (shrink)

Nonrapid eye movement (NREM) sleep is associated with fading consciousness in humans. Recent neuroimaging studies have demonstrated the spatiotemporal alterations of the brain functional connectivity (FC) in NREM sleep, suggesting the changes of information integration in the sleeping brain. However, the common stationarity assumption in FC does not satisfactorily explain the dynamic process of information integration during sleep. The dynamic FC (dFC) across brain networks is speculated to better reflect the time-varying information propagation during sleep. Accordingly, we conducted simultaneous EEG-fMRI (...) recordings involving 12 healthy men during sleep and observed dFC across sleep stages using the sliding-window approach. We divided dFC into two aspects: mean dFC (dFCmean) and variance dFC (dFCvar). A high dFCmean indicates stable brain network integrity, whereas a high dFCvar indicates instability of information transfer within and between functional networks. For the network-based dFC, the dFCvar were negatively correlated with the dFCmean across the waking and three NREM sleep stages. As sleep deepened, the dFCmean decreased (N0~N1 > N2 > N3), whereas the dFCvar peaked during the N2 stage (N0~N1 < N3 < N2). The highest dFCvar during the N2 stage indicated the unstable synchronizations across the entire brain. In the N3 stage, the overall disrupted network integration was observed through the lowest dFCmean and elevated dFCvar, compared with N0 and N1. Conclusively, when the network specificity (dFCmean) breaks down, the consciousness dissipates with increasing variability of information exchange (dFCvar). (shrink)

Sertraline is one of the most commonly prescribed antidepressants. Major depressive disorder (MDD) is characterized by spontaneous thoughts that are laden with negative affect-a "malignant sadness". Prior neuroimaging studies have identified abnormal resting-state functional connectivity (rsFC) in the spontaneous brain networks of MDD patients. But how antidepressant medication acts to relieve the experience of depression as well as adjust its associated spontaneous networks and mood-regulation circuits remains an open question. In this study, we recruited 22 drug-naïve MDD patients along with (...) 35 normal controls and investigated whether the functional integrity of cortical networks associated with spontaneous thoughts is modulated by sertraline treatment. We attempted to predict post-treatment effects based upon what we observed in the pre-treatment rsFC of drug-naïve MDD patients. In the result, we demonstrated that (1) after the sertraline treatment, the medial temporal lobe of default network (DNMTL) and mood regulation pathway-the fronto-parietal control network (FPCN), the thalamus, and the salience network (SN)-were restored to normal connectivity, relative to the pre-treatment condition; however, the altered connections of FPCN-core DN (DNCORE), FPCN-SN, and intra-FPCN among MDD patients remained impaired; (2) thalamo-prefrontal connectivity provides moderate predictive power (r2 = 0.63) for the effectiveness of sertraline treatment. In summary, our findings contribute to a body of evidence that suggests salubrious effects of sertraline treatment primarily involve the FPCN-thalamus-SN pathway. The pre-treatment rsFC in this pathway could serve as a predictor of sertraline treatment outcome. (shrink)

The brain’s intrinsic activity plays a fundamental role in its function. In normal conditions this activity is responsive to behavioural context, changing as an individual switches between directed tasks and task‐free conditions. A key feature of such changes is the movement of the brain between corresponding critical and sub‐critical states, with these dynamics supporting efficient cognitive processing. Breakdowns in processing efficiency can occur, however, in brain disorders such as depression. It was therefore hypothesised that depressive symptoms would be related to (...) reduced intrinsic activity responsiveness to changes in behavioural state. This was tested in a mixed group of major depressive disorder patients (n = 26) and healthy participants (n = 37) by measuring intrinsic EEG activity temporal structure, quantified with detrended fluctuation analysis (DFA), in eyes‐closed and eyes‐open task‐free states and contrasting between the conditions. The degree to which DFA values changed between the states was found to be negatively correlated with depressive symptoms. DFA values did not differ between states at all in those with higher symptom levels, meaning that the brain remained in a less flexible sub‐critical condition. This sub‐critical condition in the eyes‐closed state was further found to correlate with levels of maladaptive rumination. This may reflect a general cognitive inflexibility resulting from a lack in neural activity reactivity that may predispose people to overly engage in self‐directed attention. These results provide an initial link between intrinsic activity reactivity and psychological features found in psychiatric disorders. (shrink)

Some theories of consciousness emphasize its relationship to language, its emergent quality, and its causal role. Prominent among these theories is the one that Dennett has been developing for nearly four decades. According to Dennett’s most recent version, consciousness is a kind of cerebral clout. But consideration of examples of pain—arguably the best candidate on offer for a paradigm of consciousness—reveals that clout is neither necessary nor sufficient for consciousness. Moreover, pain doesn’t necessarily have the aftermath that is predicted by (...) Dennett’s Clout Theory (CT); pain cannot always be accommodated by Dennett’s methodology; and, pain does not always conform to Dennett’s proposed ontology. Dennett might wish to substitute episodic memory as a preferred paradigm for consciousness, but episodic memory is shown to be non-essential. And, were it to be treated as a paradigm of consciousness, it would create new explanatory problems for CT. Rather than abandoning CT, because it does seem to help explain some pain phenomena and because it does comport well with certain views of language, I propose that some of its more intriguing proposals be retained and treated as hypotheses to guide further empirical inquiry. Finally, I recommend some specific empirical cases wherein relevant research might be pursued. (shrink)

Cerebrospinal fluid (CSF) is a fluidic part of the brain’s microenvironment that isolates the brain from the rest of the body. CSF dilutes metabolites from neuronal activities and removes them from the brain. Its production and resorption are regulated dynamically and are central to maintaining brain homeostasis. We discovered that the major CSF source, the choroid plexus (CP), harbors the brain’s strongest circadian clock. Here, we consider some implications of the CP circadian clock for metabolite clearance in the brain. If (...) the circadian clock contributes to timed production of the CSF, its synchronization with sleep timing can maximize clearance efficiency and help prevent neurodegenerative diseases such as Alzheimer’s disease. (shrink)

Patient suffering of major depressive disorder (MDD) often complain that subjective time seems to “drag” with respect to physical time. This may point toward a generalized dysfunction of temporal processing in MDD. In the present study, we investigated temporal preparation in MDD. “Temporal preparation” refers to an increased readiness to act before an expected event; consequently, reaction time should be reduced. MDD patients and age-matched controls were required to make a saccadic eye movement between a central and an eccentric visual (...) target after a variable duration preparatory period. We found that MDD patients produced a larger number of premature saccades, saccades initiated prior to the appearance of the expected stimulus. These saccades were not temporally controlled; instead, they seemed to reflect reduced inhibitory control causing oculomotor impulsivity. In contrast, the latency of visually guided saccades was strongly influenced by temporal preparation in controls; significantly less so, in MDD patients. This observed reduced temporal preparation in MDD was associated with a faster decay of short-term temporal memory. Moreover, in patients producing a lot of premature responses, temporal preparation to early imperative stimuli was increased. In conclusion, reduced temporal preparation and short-term temporal memory in the oculomotor domain supports the hypothesis that temporal processing was altered in MDD patients. Moreover, oculomotor impulsivity interacted with temporal preparation. These observed deficits could reflect other underlying aspects of abnormal time experience in MDD. (shrink)

Susceptibility to the rubber hand illusion (RHI) varies. To date, however, there is no consensus explanation of this variability. Previous studies, focused on the role of multisensory integration, have searched for neural correlates of the illusion. But those studies have failed to identify a sufficient set of functionally specific neural correlates. Because some evidence suggests that frontal α power is one means of tracking neural instantiations of self, we hypothesized that the higher the frontal α power during the eyes-closed resting (...) state, the more stable the self. As a corollary, we infer that the more stable the self, the less susceptible are participants to a blurring of boundaries—to feeling that the rubber hand belongs to them. Indeed, we found that frontal α amplitude oscillations negatively correlate with susceptibility. Moreover, since lower frequencies often modulate higher frequencies, we explored the possibility that this might be the case for the RHI. Indeed, some evidence suggests that high frontal α power observed in low-RHI participants is modulated by δ frequency oscillations. We conclude that while neural correlates of multisensory integration might be necessary for the RHI, sufficient explanation involves variable intrinsic neural activity that modulates how the brain responds to incompatible sensory stimuli. (shrink)

Objective: Alterations in psychomotor dimension cut across different psychiatric disorders, such as schizophrenia (SCZ) and bipolar disorder (BD). This preliminary study aimed to investigate the organization of intrinsic brain activity in the subcortical-cortical sensorimotor system in SCZ (and BD) as characterized according to psychomotor dimension. -/- Method: In this resting-state functional magnetic resonance imaging (fMRI) study, functional connectivity (FC) between thalamus and sensorimotor network (SMN), along with FC from substantia nigra (SN) and raphe nuclei (RN) to basal ganglia (BG) and (...) thalamic regions, were investigated by using an a-priori-driven and dimensional approach. This was done in two datasets: SCZ patients showing inhibited psychomotricity (n = 18) vs. controls (n = 19); SCZ patients showing excited psychomotricity (n = 20) vs. controls (n = 108). Data from a third dataset of BD in inhibited depressive or manic phases (reflecting inhibited or excited psychomotricity) were used as control. -/- Results: SCZ patients suffering from psychomotor inhibition showed decreased thalamus-SMN FC toward around-zero values paralleled by a concomitant reduction of SN-BG/thalamus FC and RN-BG/thalamus FC (as BD patients in inhibited depression). By contrast, SCZ patients suffering from psychomotor excitation exhibited increased thalamus-SMN FC toward positive values paralleled by a concomitant reduction of RN-BG/thalamus FC (as BD patients in mania). -/- Conclusions: These findings suggest that patients exhibiting low or high levels of psychomotor activity show distinct patterns of thalamus-SMN coupling, which could be traced to specific deficit in SN- or RN-related connectivity. Notably, this was independent from the diagnosis of SCZ or BD, supporting an RDoC-like dimensional approach to psychomotricity. (shrink)