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:The thalamus has complex connections with the cortex and is involved in various cognitive processes. Despite increasing interest in the thalamus and the underlying thalamo-cortical interaction, little is known about thalamo-cortical connections after paediatric arterial ischaemic stroke. Therefore, the aim of this study was to investigate thalamo-cortical connections and their association with cognitive performance after arterial ischaemic stroke. Twenty patients in the chronic phase after paediatric arterial ischaemic stroke (≥2 years after diagnosis, diagnosed <16 years; aged 5-23 years, mean: 15.1 years) and 20 healthy controls matched for age and sex were examined in a cross-sectional study design. Cognitive performance (selective attention, inhibition, working memory, and cognitive flexibility) was evaluated using standardized neuropsychological tests. Resting-state functional magnetic resonance imaging was used to examine functional thalamo-cortical connectivity. Lesion masks were integrated in the preprocessing pipeline to ensure that structurally damaged voxels did not influence functional connectivity analyses. Cognitive performance (selective attention, inhibition, and working memory) was significantly reduced in patients compared to controls. Network analyses revealed significantly lower thalamo-cortical connectivity for the motor, auditory, visual, default mode network, salience, left/right executive, and dorsal attention network in patients compared with controls. Interestingly, analyses additionally revealed higher thalamo-cortical connectivity in some subdivisions of the thalamus for the default mode network (medial nuclei), motor (lateral nuclei), dorsal attention (anterior nuclei), and the left executive network (posterior nuclei) in patients compared with controls. Increased and decreased thalamo-cortical connectivity strength within the same networks was, however, found in different thalamic subdivisions. Thus, alterations in thalamo-cortical connectivity strength after paediatric stroke seem to point in both directions, with stronger as well as weaker thalamo-cortical connectivity in patients compared with controls. Multivariate linear regression, with lesion size and age as covariates, revealed significant correlations between cognitive performance (selective attention, inhibition, and working memory) and the strength of thalamo-cortical connectivity in the motor, auditory, visual, default mode network, posterior default mode network, salience, left/right executive, and dorsal attention network after childhood stroke. Our data suggest that the interaction between different sub-nuclei of the thalamus and several cortical networks relates to post-stroke cognition. The variability in cognitive outcomes after paediatric stroke might partly be explained by functional thalamo-cortical connectivity strength.
| S-EPMC9122536 | biostudies-literature
Project description:IntroductionSome previous studies in patients with lung cancer have mainly focused on exploring the cognitive dysfunction and deficits of brain function associated with chemotherapy. However, little is known about functional brain alterations that might occur prior to chemotherapy. Therefore, this study aimed to evaluate brain functional changes in patients with nonchemotherapy before chemotherapy with non-small cell lung cancer (NSCLC).MethodsResting-state functional MRI data of 35 patients with NSCLC and 46 matched healthy controls (HCs) were acquired to construct functional brain networks. Graph theoretical analysis was then applied to investigate the differences of the network and nodal measures between groups. Finally, the receiver operating characteristic (ROC) curve analysis was performed to distinguish between NSCLC and HC.ResultsDecreased nodal strength was found in the left inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part), inferior occipital gyrus, and right inferior frontal gyrus (triangular part) of patients with NSCLC while increased nodal strength was found in the right pallidum and thalamus. NSCLC also showed decreased nodal betweenness in the right superior occipital gyrus. Different hub regions distribution was found between groups, however, no hub regions showed group differences in the nodal measures. Furthermore, the ROC curve analysis showed good performance in distinguishing NSCLC from HC.ConclusionThese results suggested that topological abnormalities of pallido-thalamo-cortical circuit in functional brain network might be related to NSCLC prior to chemotherapy, which provided new insights concerning the pathophysiological mechanisms of NSCLC and could serve as promising biological markers for the identification of patients with NSCLC.
| S-EPMC8860807 | 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