Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness.
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ABSTRACT:
SUBMITTER: Sontheimer A
PROVIDER: S-EPMC7999530 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveWe employed functional MRI (fMRI) to assess whether (1) patients with disorders of consciousness (DOC) retain the ability to willfully engage in top-down processing and (2) what neurophysiologic factors distinguish patients who can demonstrate this ability from patients who cannot.MethodsSixteen volunteers, 8 patients in vegetative state (VS), 16 minimally conscious patients (MCS), and 4 exit from MCS (eMCS) patients were enrolled in a prospective cross-sectional fMRI study. Participants performed a target detection task in which they counted the number of times a (changing) target word was presented amidst a set of distractors.ResultsThree of 8 patients diagnosed as being in a VS exhibited significant activations in response to the task, thereby demonstrating a state of consciousness. Differential activations across tasks were also observed in 6 MCS patients and 1 eMCS patient. A psycho-physiologic interaction analysis revealed that the main factor distinguishing patients who responded to the task from those who did not was a greater connectivity between the anterior section of thalamus and prefrontal cortex.ConclusionsIn our sample of patients, the dissociation between overt behavior observable in clinical assessments and residual cognitive faculties is prevalent among DOC patients (37%). A substantial number of patients, including some diagnosed with VS, can demonstrate willful engagement in top-down cognition. While neuroimaging data are not the same as observable behavior, this suggests that the mental status of some VS patients exceeds what can be appreciated clinically. Furthermore, thalamo-frontal circuits might be crucial to sustaining top-down functions.
| S-EPMC4336082 | biostudies-literature
Project description:Recent evidence suggests that the quantity and quality of conscious experience may be a function of the complexity of activity in the brain and that consciousness emerges in a critical zone between low and high-entropy states. We propose fractal shapes as a measure of proximity to this critical point, as fractal dimension encodes information about complexity beyond simple entropy or randomness, and fractal structures are known to emerge in systems nearing a critical point. To validate this, we tested several measures of fractal dimension on the brain activity from healthy volunteers and patients with disorders of consciousness of varying severity. We used a Compact Box Burning algorithm to compute the fractal dimension of cortical functional connectivity networks as well as computing the fractal dimension of the associated adjacency matrices using a 2D box-counting algorithm. To test whether brain activity is fractal in time as well as space, we used the Higuchi temporal fractal dimension on BOLD time-series. We found significant decreases in the fractal dimension between healthy volunteers (n = 15), patients in a minimally conscious state (n = 10), and patients in a vegetative state (n = 8), regardless of the mechanism of injury. We also found significant decreases in adjacency matrix fractal dimension and Higuchi temporal fractal dimension, which correlated with decreasing level of consciousness. These results suggest that cortical functional connectivity networks display fractal character and that this is associated with level of consciousness in a clinically relevant population, with higher fractal dimensions (i.e. more complex) networks being associated with higher levels of consciousness. This supports the hypothesis that level of consciousness and system complexity are positively associated, and is consistent with previous EEG, MEG, and fMRI studies.
| S-EPMC7017993 | biostudies-literature
Project description:ObjectiveGrowing evidence has implicated dysfunction of the thalamus and its projection cortical targets in depression. However, the anatomical specificity of thalamo-cortical connectivity in major depressive disorder (MDD) remains unknown due to the regional heterogeneity of the thalamus and limited methods to examine this.MethodsResting-state fMRI was collected on 70 MDD patients and 70 healthy controls. The thalamus was parcellated based on connectivity with six predefined cortical regions of interest (ROIs). The segmented thalamic nuclei were used as seeds to map connectivity with the rest of the whole brain. The cortical-to-thalamus connectivity values and thalamus-based connectivity maps were compared between groups.ResultsThe cortical ROIs demonstrated correlations with spatially distinct zones within the thalamus. We found a trend toward reduced parietal ROI-to-thalamus connectivity in MDD. Importantly, MDD patients demonstrated reduced connectivity between prefrontal and parietal thalamus ROIs and bilateral middle frontal gyrus (MFG) and the right posterior default mode network (DMN) and between the prefrontal and motor thalamus ROIs and lateral temporal regions. Conversely, increased connectivity emerged between the motor thalamus ROI and right MFG and right medial frontal gyrus/anterior cingulate; between motor/somatosensory thalamus ROIs and right posterior DMN; between prefrontal/somatosensory thalamus ROIs and cerebellum; and between the parietal thalamus ROI and left insula.ConclusionsThis study is the first to examine the anatomical specificity of thalamo-cortical connectivity disturbances in MDD. Subjects with MDD demonstrated altered thalamo-cortical connectivity characterized by a complex pattern of region-dependent hypo- or hyperconnectivity. We therefore speculate that selectively modulating the connectivity of thalamo-cortical circuitry may be a potential novel therapeutic mechanism for MDD.
| S-EPMC6490069 | biostudies-literature
Project description:Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has been shown to alter cortical excitability and activity via application of weak direct currents. Beyond intracortical effects, functional imaging as well as behavioral studies are suggesting additional tDCS-driven alterations of subcortical areas, however, direct evidence for such effects is scarce. We aimed to investigate the impact of tDCS on cortico-subcortical functional networks by seed functional connectivity analysis of different striatal and thalamic regions to prove tDCS-induced alterations of the cortico-striato-thalamic circuit. fMRI resting state data sets were acquired immediately before and after 10 min of bipolar tDCS during rest, with the anode/cathode placed over the left primary motor cortex (M1) and the cathode/anode over the contralateral frontopolar cortex. To control for possible placebo effects, an additional sham stimulation session was carried out. Functional coupling between the left thalamus and the ipsilateral primary motor cortex (M1) significantly increased following anodal stimulation over M1. Additionally, functional connectivity between the left caudate nucleus and parietal association cortices was significantly strengthened. In contrast, cathodal tDCS over M1 decreased functional coupling between left M1 and contralateral putamen. In summary, in this study, we show for the first time that tDCS modulates functional connectivity of cortico-striatal and thalamo-cortical circuits. Here we highlight that anodal tDCS over M1 is capable of modulating elements of the cortico-striato-thalamo-cortical functional motor circuit.
| S-EPMC6870027 | biostudies-literature
Project description:Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to research abnormal functional connectivity (FC) in patients with disorders of consciousness (DOC). However, most studies assumed steady spatial-temporal signal interactions between distinct brain regions during the scan period. The aim of this study was to explore abnormal dynamic functional connectivity (dFC) in DOC patients. After excluding 26 patients' data that failed to meet the requirements of imaging quality, we retained 19 DOC patients (12 with unresponsive wakefulness syndrome and 7 in a minimally conscious state, diagnosed with the Coma Recovery Scale-Revised [CRS-R]) for the dFC analysis. We used the sliding windows approach to construct dFC matrices. Then these matrices were clustered into distinct states using the k-means clustering algorithm. We found that the DOC patients showed decreased dFC in the sensory and somatomotor networks compared with the healthy controls. There were also significant differences in temporal properties, the mean dwell time (MDT) and the number of transitions (NT), between the DOC patients and the healthy controls. In addition, we also used a hidden Markov model (HMM) to test the robustness of the results. With the connectome-based predictive modeling (CPM) approach, we found that the properties of abnormal dynamic network can be used to predict the CRS-R scores of the patients after severe brain injury. These findings may contribute to a better understanding of the abnormal brain networks in DOC patients.
| S-EPMC6881656 | biostudies-literature
Project description:Over the last 20 years, studies have provided greater insight into disorders of consciousness (DOC), also known as altered state of consciousness. Increased brain residual functions have been identified in patients with DOC due to the successful application of novel next-generation imaging technologies. Many unconscious patients have now been confirmed to retain considerable cognitive functions. It is hoped that greater insight regarding the psychological state of patients may be achieved through the use of functional magnetic resonance imaging and brain-computer interfaces. However, issues surrounding the research and treatment of DOC remain problematic. These include differing opinions on the definition of consciousness, difficulties in diagnosis, assessment, prognosis and/or treatment, and newly emerging ethical, legal and social issues. To overcome these, appropriate care must be offered to patients with DOC by clinicians and families, as DOC patients may now be considered to live in more than just a vegetative state. The present article reviews the controversy surrounding the definition of consciousness and the reliability of novel technologies, prognostic prediction, communication with DOC patients and treatment methods. The ethical and social issues surrounding the treatment of DOC and future perspectives are also considered.
| S-EPMC5526117 | biostudies-other
Project description:Functional changes in the brain of patients with painful diabetic neuropathy (PDN) have remained largely elusive. The aim of the present study was to explore changes in thalamo-cortical functional connectivity (FC) of patients with PDN using resting-state functional MRI. A total of 20 patients with type 2 diabetes mellitus (T2DM) with non-painful diabetic neuropathy (Group NDN), 19 patients with T2DM with PDN (Group-PDN) and 13 age-, sex- and education-matched healthy controls were recruited. The differences in thalamo-cortical FC among the three groups were compared. Patients in Group PDN had increased FC in the left thalamus, the right angular gyrus and the occipital gyrus as compared to those in Group NDN. Furthermore, patients in Group PDN had increased FC in the right thalamus and angular gyrus as compared to those in Group NDN. In conclusion, the present results suggested that the thalamo-cortical FC is increased in patients with T2DM and PDN. Furthermore, the increased FC in the thalamic-parietal-occipital connectivity may be a central pathophysiological mechanism for PDN. The study was retrospectively registered at ClinicalTrials.gov on 3 October 2018 (identifier no. NCT03700502).
| S-EPMC8005696 | biostudies-literature
Project description:INTRODUCTION:Functional connectivity alterations within individual resting state networks (RSNs) are linked to disorders of consciousness (DOC). If these alterations influence the interaction quality with other RNSs, then, brain alterations in patients with DOC would be characterized by connectivity changes in the large-scale model composed of RSNs. How are functional interactions between RSNs influenced by internal alterations of individual RSNs? Do the functional alterations induced by DOC change some key properties of the large-scale network, which have been suggested to be critical for the consciousness emergence? Here, we use network analysis to measure functional connectivity in patients with DOC and address these questions. We hypothesized that network properties provide descriptions of brain functional reconfiguration associated with consciousness alterations. METHODS:We apply nodal and global network measurements to study the reconfiguration linked with the disease severity. We study changes in integration, segregation, and centrality properties of the functional connectivity between the RSNs in subjects with different levels of consciousness. RESULTS:Our analysis indicates that nodal measurements are more sensitive to disease severity than global measurements, particularly, for functional connectivity of sensory and cognitively related RSNs. CONCLUSION:The network property alterations of functional connectivity in different consciousness levels suggest a whole-brain topological reorganization of the large-scale functional connectivity in patients with DOC.
| S-EPMC6955826 | biostudies-literature
Project description:Disorders of consciousness are impaired states of consciousness caused by severe brain injuries. Previous resting-state functional magnetic resonance imaging studies have reported abnormal brain network properties at different topological scales in patients with disorders of consciousness by using graph theoretical analysis. However, it is still unclear how inter-regional directed propagation activities affect the topological organization of functional brain networks in patients with disorders of consciousness. To reveal the altered topological organization in patients with disorders of consciousness, we constructed whole-brain directed functional networks by combining functional connectivity analysis and time delay estimation. Then we performed graph theoretical analysis based on the directed functional brain networks at three topological scales, from the nodal scale, the resting-state network scale to the global scale. Finally, the canonical correlation analysis was used to determine the correlations between altered topological properties and clinical scores in patients with disorders of consciousness. At the nodal scale, we observed decreased in-degree and increased out-degree in the precuneus in patients with disorders of consciousness. At the resting-state network scale, the patients with disorders of consciousness showed reorganized motif patterns within the default mode network and between the default mode network and other resting-state networks. At the global scale, we found a lower global clustering coefficient in the patients with disorders of consciousness than in the controls. The results of the canonical correlation analysis showed that the abnormal degree and the disrupted motif were significantly correlated with the clinical scores of the patients with disorders of consciousness. Our findings showed that consciousness impairment can be revealed by abnormal directed connection patterns at multiple topological scales in the whole brain, and the disrupted directed connection patterns may serve as clinical biomarkers to assess the dysfunction of patients with disorders of consciousness.
| S-EPMC10066573 | biostudies-literature
Project description:Ongoing changes in arousal influence sensory processing and behavioral performance. Yet the circuit-level correlates for this influence remain poorly understood. Here, we investigate how functional interaction between posterior parietal cortex (PPC) and lateral posterior (LP)/Pulvinar is influenced by ongoing fluctuations in pupil-linked arousal, which is a non-invasive measure of neuromodulatory tone in the brain. We find that fluctuations in pupil-linked arousal correlate with changes to PPC to LP/Pulvinar oscillatory interaction, with cortical alpha oscillations driving activity during low arousal states, and LP/Pulvinar driving PPC in the theta frequency band during higher arousal states. Active visual exploration by saccadic eye movements elicits similar transitions in thalamo-cortical interaction. Furthermore, the presentation of naturalistic video stimuli induces thalamo-cortical network states closely resembling epochs of high arousal in the absence of visual input. Thus, neuromodulators may play a role in dynamically sculpting the patterns of thalamo-cortical functional interaction that underlie visual processing.
| S-EPMC6018110 | biostudies-literature