Fractal Dimension of Cortical Functional Connectivity Networks Predicts Severity in Disorders of Consciousness

AbstractRecent 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 on the axes of order/randomness and integration/differentiation. 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 the 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 predictive of level of consciousness in a clinically relevant population, with more fractal (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.

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Serotonergic Psychedelics LSD & Psilocybin Increase the Fractal Dimension of Cortical Brain Activity in Spatial and Temporal Domains

10.1101/517847 ◽

2019 ◽

Cited By ~ 4

Author(s):

TF Varley ◽

R Carhart-Harris ◽

Leor Roseman ◽

David K Menon ◽

EA Stamatakis

Keyword(s):

Fractal Dimension ◽

Functional Connectivity ◽

Critical Point ◽

Fractal Structure ◽

Brain Activity ◽

Past Research ◽

Psychedelic Drugs ◽

Thought Patterns ◽

The Mind ◽

The Brain

AbstractPsychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers in-vestigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attentional network. These results show that psychedelic drugs increase the fractal character of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.Author SummaryThe unique state of consciousness produced by psychedelic drugs like LSD and psilocybin (the active component in magic mushrooms) are potentially useful tools for discovering how specific changes in the brain are related to differences in perception and thought patterns. Past research into the neuroscience of psychedelics has led to the proposal of a general theory of brain function and consciousness: the Entropic Brain Hypothesis proposes that consciousness emerges when the brain is sitting near a critical tipping point between order and chaos and that the mind-expanding elements of the psychedelic experience are caused by the brain moving closer to that critical transition point. Physicists have discovered that near this critical point, many different kinds of systems, from magnets to ecosystems, take on a distinct, fractal structure. Here, we used two measures of fractal-quality of brain activity, as seen in fMRI, to test whether the activity of the brain on psychedelics is more fractal than normal. We found evidence that this is the case and interpret that as supporting the theory that, psychedelic drugs are move the brain towards a more critical state.

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Pain Perception in Disorder of Consciousness: A Scoping Review on Current Knowledge, Clinical Applications, and Future Perspective

Brain Sciences ◽

10.3390/brainsci11050665 ◽

2021 ◽

Vol 11 (5) ◽

pp. 665

Author(s):

Rocco Salvatore Calabrò ◽

Loris Pignolo ◽

Claudia Müller-Eising ◽

Antonino Naro

Keyword(s):

Functional Connectivity ◽

Scoping Review ◽

Pain Perception ◽

Current Knowledge ◽

Conscious Experience ◽

Minimally Conscious State ◽

Conscious State ◽

Future Perspective ◽

Disorder Of Consciousness ◽

Minimally Conscious

Pain perception in individuals with prolonged disorders of consciousness (PDOC) is still a matter of debate. Advanced neuroimaging studies suggest some cortical activations even in patients with unresponsive wakefulness syndrome (UWS) compared to those with a minimally conscious state (MCS). Therefore, pain perception has to be considered even in individuals with UWS. However, advanced neuroimaging assessment can be challenging to conduct, and its findings are sometimes difficult to be interpreted. Conversely, multichannel electroencephalography (EEG) and laser-evoked potentials (LEPs) can be carried out quickly and are more adaptable to the clinical needs. In this scoping review, we dealt with the neurophysiological basis underpinning pain in PDOC, pointing out how pain perception assessment in these individuals might help in reducing the misdiagnosis rate. The available literature data suggest that patients with UWS show a more severe functional connectivity breakdown among the pain-related brain areas compared to individuals in MCS, pointing out that pain perception increases with the level of consciousness. However, there are noteworthy exceptions, because some UWS patients show pain-related cortical activations that partially overlap those observed in MCS individuals. This suggests that some patients with UWS may have residual brain functional connectivity supporting the somatosensory, affective, and cognitive aspects of pain processing (i.e., a conscious experience of the unpleasantness of pain), rather than only being able to show autonomic responses to potentially harmful stimuli. Therefore, the significance of the neurophysiological approach to pain perception in PDOC seems to be clear, and despite some methodological caveats (including intensity of stimulation, multimodal paradigms, and active vs. passive stimulation protocols), remain to be solved. To summarize, an accurate clinical and neurophysiological assessment should always be performed for a better understanding of pain perception neurophysiological underpinnings, a more precise differential diagnosis at the level of individual cases as well as group comparisons, and patient-tailored management.

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Effect of Retinohypothalamic Tract Dysfunction on Melatonin Level in Patients with Chronic Disorders of Consciousness

Brain Sciences ◽

10.3390/brainsci11050559 ◽

2021 ◽

Vol 11 (5) ◽

pp. 559

Author(s):

Mikhail Kanarskii ◽

Julia Nekrasova ◽

Svetlana Vitkovskaya ◽

Pranil Pradhan ◽

Sergey Peshkov ◽

...

Keyword(s):

Healthy Volunteers ◽

Direct Relationship ◽

Disorders Of Consciousness ◽

Melatonin Level ◽

Melatonin Secretion ◽

Peripheral Part ◽

Level Of Consciousness ◽

Retinohypothalamic Tract ◽

Chronic Disorders ◽

Chronic Disorders Of Consciousness

Objective: The aim of this study is to compare the secretion level of nocturnal melatonin and the characteristics of the peripheral part of the visual analyzer in patients with chronic disorders of consciousness (DOC). Materials and Methods: We studied the level of melatonin in 22 patients with chronic DOC and in 11 healthy volunteers. The fundus condition was assessed using the ophthalmoscopic method. Results: The average level of nocturnal melatonin in patients with DOC differed by 80% from the level of indole in healthy volunteers. This reveals a direct relationship between etiology, the level of consciousness, gaze fixation, coma recovery scale-revised score and the level of melatonin secretion. Examination by an ophthalmologist revealed a decrease in the macular reflex in a significant number of DOC patients, which in turn correlates negatively with the time from brain injury and positively with low values of nocturnal melatonin.

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Evaluation of structural variations in the pituitary gland, hormonal status and laboratory markers of the central nervous system functioning in patients with chronic disorders of consciousness

Journal of obstetrics and women s diseases ◽

10.17816/jowd77930 ◽

2021 ◽

Vol 70 (5) ◽

pp. 23-36

Author(s):

Ekaterina A. Kondratyeva ◽

Alina O. Ivanova ◽

Maria I. Yarmolinskaya ◽

Elena G. Potyomkina ◽

Natalya V. Dryagina ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Blood Serum ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Unresponsive Wakefulness Syndrome ◽

Level Of Consciousness ◽

Chronic Disorders ◽

Minimally Conscious ◽

Chronic Disorders Of Consciousness

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation. AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness. MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid. RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state. CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.

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Computerized physical and cognitive training improves the functional architecture of the brain in adults with Down syndrome: A network science EEG study

Network Neuroscience ◽

10.1162/netn_a_00177 ◽

2020 ◽

pp. 1-21

Author(s):

Alexandra Anagnostopoulou ◽

Charis Styliadis ◽

Panagiotis Kartsidis ◽

Evangelia Romanopoulou ◽

Vasiliki Zilidou ◽

...

Keyword(s):

Down Syndrome ◽

Functional Connectivity ◽

Cognitive Training ◽

Resting State ◽

Network Architecture ◽

Right Hemisphere ◽

Random Network ◽

Brain Activity ◽

Hierarchical Organization ◽

The Brain

Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.

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Non-Invasive Rhythmic Musical-Electric Trigeminal Nerve Stimulation Improves Consciousness in Patients with Disorders of Consciousness

10.21203/rs.3.rs-256846/v1 ◽

2021 ◽

Author(s):

Min Wu ◽

Benyan Luo ◽

Yamei Yu ◽

Xiaoxia Li ◽

Jian Gao ◽

...

Keyword(s):

Trigeminal Nerve ◽

Nerve Stimulation ◽

Brain Activity ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Non Invasive ◽

Trigeminal Nerve Stimulation ◽

Novel Approach ◽

Minimally Conscious

Abstract Disorders of consciousness (DOC) are often accompanied by aberrant oscillatory neural activity in the thalamus and cerebral cortex. Patient-friendly non-invasive treatments targeting this functional anomaly are still missing. We propose and validate a novel approach that aims to restore DOC patients’ thalamocortical oscillations by combining rhythmic trigeminal-nerve stimulation (TNS) with comodulated musical stimulation. In a cluster-randomized, placebo-controlled, double-blinded, pretest-posttest clinical study, we show that application of this multisensory approach for 40 min on five consecutive days reliably leads to long-lasting improvements in DOC patients’ consciousness (assessed with Coma Recovery Scale-Revised) and oscillatory brain activity at the musical-electric TNS frequency (assessed with electroencephalography and a novel rhythmic auditory-speech paradigm). We found diagnostic improvement in 47% of patients in minimally conscious state and a positive relationship between patients’ behavioral and neural improvements. Based on this evidence we argue that non-invasive musical-electric TNS may serve as an effective patient-friendly DOC treatment and suggest frequency-specific oscillatory neural enhancement as its mode of action.

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Neurophysiological Correlates of a Single Session of Prefrontal tDCS in Patients with Prolonged Disorders of Consciousness: A Pilot Double-Blind Randomized Controlled Study

Brain Sciences ◽

10.3390/brainsci10070469 ◽

2020 ◽

Vol 10 (7) ◽

pp. 469

Author(s):

Manon Carrière ◽

Sepehr Mortaheb ◽

Federico Raimondo ◽

Jitka Annen ◽

Alice Barra ◽

...

Keyword(s):

Brain Activity ◽

Minimally Conscious State ◽

Disorders Of Consciousness ◽

Controlled Study ◽

Phase Lag ◽

Alpha Band ◽

Group Level ◽

Single Session ◽

Double Blind ◽

Significant Treatment

Background. Transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) was reported to promote the recovery of signs of consciousness in some patients in a minimally conscious state (MCS), but its electrophysiological effects on brain activity remain poorly understood. Objective. We aimed to assess behavioral (using the Coma Recovery Scale—Revised; CRS-R) and neurophysiological effects (using high density electroencephalography; hdEEG) of lDLPFC-tDCS in patients with prolonged disorders of consciousness (DOC). Methods. In a double-blind, sham-controlled, crossover design, one active and one sham tDCS (2 mA, 20 min) were delivered in a randomized order. Directly before and after tDCS, 10 min of hdEEG were recorded and the CRS-R was administered. Results. Thirteen patients with severe brain injury were enrolled in the study. We found higher relative power at the group level after the active tDCS session in the alpha band in central regions and in the theta band over the frontal and posterior regions (uncorrected results). Higher weighted symbolic mutual information (wSMI) connectivity was found between left and right parietal regions, and higher fronto-parietal weighted phase lag index (wPLI) connectivity was found, both in the alpha band (uncorrected results). At the group level, no significant treatment effect was observed. Three patients showed behavioral improvement after the active session and one patient improved after the sham. Conclusion. We provide preliminary indications that neurophysiological changes can be observed after a single session of tDCS in patients with prolonged DOC, although they are not necessarily paralleled with significant behavioral improvements.

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Fractal Dimension as Quantifier of EEG Activity in Driving Simulation

Mathematics ◽

10.3390/math9111311 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1311

Author(s):

Mª Victoria Sebastián ◽

Mª Antonia Navascués ◽

Antonio Otal ◽

Carlos Ruiz ◽

Mª Ángeles Idiazábal ◽

...

Keyword(s):

Fractal Dimension ◽

Brain Activity ◽

Fractal Theory ◽

Driving Simulation ◽

Geometric Complexity ◽

Eeg Activity ◽

Modeling And Analysis ◽

Brain Waves ◽

Electroencephalographic Signals ◽

The Brain

Dynamical systems and fractal theory methodologies have been proved useful for the modeling and analysis of experimental datasets and, in particular, for electroencephalographic signals. The computation of the fractal dimension of approximation curves in the plane enables the assignment of numerical values to bioelectric recordings in order to discriminate between different states of the observed system. The procedure does not require the stationarity of the signals nor extremely long segments of data. In previous works, we checked that this parameter is a good index for brain activity. In this paper, we consider this measurement in order to quantify the geometric complexity of the brain waves in states of rest and during vehicle driving simulation in different scenarios. This work presents evidence that the fractal dimension allows the detection of the brain bioelectric changes produced in the areas that carry out the different driving simulation tasks, increasing with their complexity.

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Similarity of brain activity patterns during learning and subsequent resting state predicts memory consolidation

10.1101/2020.09.04.283002 ◽

2020 ◽

Author(s):

Z. Zavecz ◽

K. Janacsek ◽

P. Simor ◽

M.X. Cohen ◽

D. Nemeth

Keyword(s):

Functional Connectivity ◽

Memory Consolidation ◽

Brain Activity ◽

Serial Order ◽

Order Information ◽

Novel Approach ◽

Continuous Eeg ◽

Induced Changes ◽

Probability Information ◽

The Brain

AbstractLong-term memory depends on memory consolidation that seems to rely on learning-induced changes in the brain activity. Here, we introduced a novel approach analyzing continuous EEG data to study learning-induced changes as well as trait-like characteristics in brain activity underlying consolidation. Thirty-one healthy young adults performed a learning task and their performance was retested after a short (~1h) delay, that enabled us to investigate the consolidation of serial-order and probability information simultaneously. EEG was recorded during a pre- and post-learning rest period and during learning. To investigate the brain activity associated with consolidation performance, we quantified similarities in EEG functional connectivity of learning and pre-learning rest (baseline similarity) as well as learning and post-learning rest (post-learning similarity). While comparable patterns of these two could indicate trait-like similarities, changes in similarity from baseline to post-learning could indicate learning-induced changes, possibly spontaneous reactivation. Individuals with higher learning-induced changes in alpha frequency connectivity (8.5–9.5 Hz) showed better consolidation of serial-order information. This effect was stronger for more distant channels, highlighting the role of long-range centro-parietal networks underlying the consolidation of serial-order information. The consolidation of probability information was associated with learning-induced changes in delta frequency connectivity (2.5–3 Hz) and seemed to be dependent on more local, short-range connections. Beyond these associations with learning-induced changes, we also found substantial overlap between the baseline and post-learning similarity and their associations with consolidation performance, indicating that stable (trait-like) differences in functional connectivity networks may also be crucial for memory consolidation.Significance statementWe studied memory consolidation in humans by characterizing how similarity in neural oscillatory patterns during learning and rest periods supports consolidation. Previous studies on similarity focused on learning-induced changes (including reactivation) and neglected the stable individual characteristics that are present over resting periods and learning. Moreover, learning-induced changes are predominantly studied invasively in rodents or with neuroimaging or event-related electrophysiology techniques in humans. Here, we introduced a novel approach that enabled us 1) to reveal both learning-induced changes and trait-like individual differences in brain activity and 2) to study learning-induced changes in humans by analyzing continuous EEG. We investigated the consolidation of two types of information and revealed distinct learning-induced changes and trait-like characteristics underlying the different memory processes.

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Looking for effects of qualia on event-related brain potentials of close others in search for a cause of the similarity of qualia assumed across individuals

F1000Research ◽

10.12688/f1000research.5977.3 ◽

2018 ◽

Vol 3 ◽

pp. 316

Author(s):

Sheila Bouten ◽

Hugo Pantecouteau ◽

J. Bruno Debruille

Keyword(s):

Time Window ◽

Brain Activity ◽

Conscious Experience ◽

Event Related Potentials ◽

The Other ◽

Brain Potentials ◽

Frontal Electrode ◽

Related Potentials ◽

The Individual ◽

The Brain

Qualia, the individual instances of subjective conscious experience, are private events. However, in everyday life, we assume qualia of others and their perceptual worlds, to be similar to ours. One way this similarity is possible is if qualia of others somehow contribute to the production of qualia by our own brain and vice versa. To test this hypothesis, we focused on the mean voltages of event-related potentials (ERPs) in the time-window of the P600 component, whose amplitude correlates positively with conscious awareness. These ERPs were elicited by images of the international affective picture system in 16 pairs of friends, siblings or couples going side by side through hyperscanning without having to interact. Each of the 32 members of these 16 pairs faced one half of the screen and could not see what the other member was presented with on the other half. One stimulus occurred on each half simultaneously. The sameness of these stimulus pairs was manipulated as well as the participants’ belief in that sameness by telling subjects’ pairs that they were going to be presented with the same stimuli in two blocks and with different ones in the two others. ERPs were more positive at all electrode subsets for stimulus pairs that were inconsistent with the belief than for those that were consistent. In the N400 time window, at frontal electrode sites, ERPs were again more positive for inconsistent than for consistent stimuli. As participants had no way to see the stimulus their partner was presented with and thus no way to detect inconsistence, these data might reveal an impact of the qualia of a person on the brain activity of another. Such impact could provide a research avenue when trying to explain the similarity of qualia across individuals.

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