Zirui Huang

The self and its resting state in consciousness: An investigation of the vegetative state

Recent studies have demonstrated resting‐state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting‐state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self‐referential processing and the resting‐state activity in cortical midline regions. As such, we investigated task‐related neural activity during active self‐referential processing and various measures of resting‐state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task‐specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting‐state activity, that is functional connectivity and the amplitude of low‐frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self‐referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness. Hum Brain Mapp 35:1997–2008, 2014.

Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia

Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter‐ and intra‐regional neural synchronization and temporal variance of resting state activity in anesthetic‐induced unconsciousness state. Applying an intra‐subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra‐regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency‐dependent effects of SD in the thalamus, which showed abnormally high SD in Slow‐5 (0.01–0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp 35:5368–5378, 2014.

Contrasting variability patterns in the default mode and sensorimotor networks balance in bipolar depression and mania.

Significance Depressive and manic phases in bipolar disorder show opposite constellations of affective, cognitive, and psychomotor symptoms. These may be related to disbalance between large-scale networks, such as the default-mode (DMN) and sensorimotor network (SMN) that are involved in these functions. The variability of resting-state signal amplitude—an index of neuronal activity—of large-scale networks and their balances was investigated in bipolar disorder. The DMN/SMN balance was tilted toward the DMN in depression (characterized by excessive focus on internal thought contents and psychomotor inhibition) and toward the SMN in mania (characterized by excessive focus on external environmental contents and psychomotor overexcitement). Accordingly, the contrasting symptoms of depression and mania may be related to opposite spatiotemporal patterns in the resting-state structure. Depressive and manic phases in bipolar disorder show opposite constellations of affective, cognitive, and psychomotor symptoms. At a neural level, these may be related to topographical disbalance between large-scale networks, such as the default mode network (DMN) and sensorimotor network (SMN). We investigated topographical patterns of variability in the resting-state signal—measured by fractional SD (fSD) of the BOLD signal—of the DMN and SMN (and other networks) in two frequency bands (Slow5 and Slow4) with their ratio and clinical correlations in depressed (n = 20), manic (n = 20), euthymic (n = 20) patients, and healthy controls (n = 40). After controlling for global signal changes, the topographical balance between the DMN and SMN, specifically in the lowest frequency band, as calculated by the Slow5 fSD DMN/SMN ratio, was significantly increased in depression, whereas the same ratio was significantly decreased in mania. Additionally, Slow5 variability was increased in the DMN and decreased in the SMN in depressed patients, whereas the opposite topographical pattern was observed in mania. Finally, the Slow5 fSD DMN/SMN ratio correlated positively with clinical scores of depressive symptoms and negatively with those of mania. Results were replicated in a smaller independent bipolar disorder sample. We demonstrated topographical abnormalities in frequency-specific resting-state variability in the balance between DMN and SMN with opposing patterns in depression and mania. The Slow5 DMN/SMN ratio was tilted toward the DMN in depression but was shifted toward the SMN in mania. The Slow5 fSD DMN/SMN pattern could constitute a state-biomarker in diagnosis and therapy.

Functional connectivity and neuronal variability of resting state activity in bipolar disorder—reduction and decoupling in anterior cortical midline structures

Introduction: The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. Methods: We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01–0.10 Hz; Slow‐5: 0.01–0.027 Hz; Slow‐4: 0.027–0.073 Hz). Finally, we studied the correlations between FC alterations and clinical‐neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. Results: We found in BD decreased FC (especially in Slow‐5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC‐based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). Conclusions: These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN‐SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN‐posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD. Hum Brain Mapp 36:666–682, 2015.

Is There a Nonadditive Interaction Between Spontaneous and Evoked Activity? Phase-Dependence and Its Relation to the Temporal Structure of Scale-Free Brain Activity

Abstract The aim of our study was to use functional magnetic resonance imaging to investigate how spontaneous activity interacts with evoked activity, as well as how the temporal structure of spontaneous activity, that is, long‐range temporal correlations, relate to this interaction. Using an extremely sparse event‐related design (intertrial intervals: 52‐60 s), a novel blood oxygen level‐dependent signal correction approach (accounting for spontaneous fluctuations using pseudotrials) and phase analysis, we provided direct evidence for a nonadditive interaction between spontaneous and evoked activity. We demonstrated the discrepancy between the present and previous observations on why a linear superposition between spontaneous and evoked activity can be seen by using co‐occurring signals from homologous brain regions. Importantly, we further demonstrated that the nonadditive interaction can be characterized by phase‐dependent effects of spontaneous activity, which is closely related to the degree of long‐range temporal correlations in spontaneous activity as indexed by both power‐law exponent and phase‐amplitude coupling. Our findings not only contribute to the understanding of spontaneous brain activity and its scale‐free properties, but also bear important implications for our understanding of neural activity in general.

How are different neural networks related to consciousness

We aimed to investigate the roles of different resting‐state networks in predicting both the actual level of consciousness and its recovery in brain injury patients.

Intertrial Variability in the Premotor Cortex Accounts for Individual Differences in Peripersonal Space.

We live in a dynamic environment, constantly confronted with approaching objects that we may either avoid or be forced to address. A multisensory and sensorimotor interface, the peripersonal space (PPS), mediates every physical interaction between our body and the environment. Behavioral investigations show high variability in the extension of PPS across individuals, but there is a lack of evidence on the neural underpinnings of these large individual differences. Here, we used approaching auditory stimuli and fMRI to capture the individual boundary of PPS and examine its neural underpinnings. Precisely, we tested the hypothesis that intertrial variability (ITV) in brain regions coding PPS predicts individual differences of its boundary at the behavioral level. Selectively in the premotor cortex, we found that ITV, rather than trial-averaged amplitude, of BOLD responses to far rather than near dynamic stimuli predicts the individual extension of PPS. Our results provide the first empirical support for the relevance of ITV of brain responses for individual differences in human behavior. SIGNIFICANCE STATEMENT Peripersonal space (PPS) is a multisensory and sensorimotor interface mediating every physical interaction between the body and the environment. A major characteristic of the boundary of PPS in humans is the extremely high variability of its location across individuals. We show that interindividual differences in the extension of the PPS are predicted by variability of BOLD responses in the premotor cortex to far stimuli approaching our body. Our results provide the first empirical support to the relevance of variability of evoked responses for human behavior and its variance across individuals.

Increase in glutamate/glutamine concentration in the medial prefrontal cortex during mental imagery: A combined functional mrs and fMRI study

Recent functional magnetic resonance spectroscopy (fMRS) studies have shown changes in glutamate/glutamine (Glx) concentrations between resting‐state and active‐task conditions. However, the types of task used have been limited to sensory paradigms, and the regions from which Glx concentrations have been measured limited to sensory ones. This leaves open the question as to whether the same effect can be seen in higher‐order brain regions during cognitive tasks. Cortical midline structures, especially the medial prefrontal cortex (MPFC), have been suggested to be involved in various such cognitive tasks. We, therefore set out to use fMRS to investigate the dynamics of Glx concentrations in the MPFC between resting‐state and mental imagery task conditions. The auditory cortex was used as a control region. In addition, functional magnetic resonance imaging was used to explore task‐related neural activity changes. The mental imagery task consisted of imagining swimming and was applied to a large sample of healthy participants (n = 46). The participants were all competitive swimmers, ensuring proficiency in mental‐swimming. Glx concentrations in the MPFC increased during the imagery task, as compared to resting‐state periods preceding and following the task. These increases mirror BOLD activity changes in the same region during the task. No changes in either Glx concentrations or BOLD activity were seen in the auditory cortex. These findings contribute to our understanding of the biochemical basis of generating or manipulating mental representations and the MPFCs role in this. Hum Brain Mapp 36:3204–3212, 2015.

VERBAL MEMORY RETRIEVAL ENGAGES VISUAL CORTEX IN MUSICIANS

As one major line of research on brain plasticity, many imaging studies have been conducted to identify the functional and structural reorganization associated with musical expertise. Based on previous behavioral research, the present study used functional magnetic resonance imaging to identify the neural correlates of superior verbal memory performance in musicians. Participants with and without musical training performed a verbal memory task to first encode a list of words auditorily delivered and then silently recall as many words as possible. They performed in separate blocks a control task involving pure tone pitch judgment. Post-scan recognition test showed better memory performance in musicians than non-musicians. During memory retrieval, the musicians showed significantly greater activations in bilateral though left-lateralized visual cortex relative to the pitch judgment baseline. In comparison, no such visual cortical activations were found in the non-musicians. No group differences were observed during the encoding stage. The results echo a previous report of visual cortical activation during verbal memory retrieval in the absence of any visual sensory stimulation in the blind population, who are also known to possess superior verbal memory. It is suggested that the visual cortex can be recruited to serve as extra memory resources and contributes to the superior verbal memory in special situations. While in the blind population, such cross-modal functional reorganization may be induced by sensory deprivation; in the musicians it may be induced by the long-term and demanding nature of musical training to use as much available neural resources as possible.

Reduced Resting-State Functional Connectivity of the Somatosensory Cortex Predicts Psychopathological Symptoms in Women with Bulimia Nervosa

Background: Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. Methods: Sixteen medication-free women with BN (age = 23 ± 5 years) and 18 matched controls (age = 23 ± 3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. Results: Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t = 9.0, df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r = −0.4; P = 0.02) and interoceptive awareness (r = −0.4; P = 0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. Conclusion: Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.