An official website of the United States government
Neuronal activity propagates through the network during seizures, engaging brain dynamics at multiple scales. Such propagating events can be described through the avalanches framework, which can relate spatiotemporal activity at the microscale with global network properties. Interestingly, propagating avalanches in healthy networks are indicative of critical dynamics, where the network is organized to a phase transition, which optimizes certain computational properties. Some have hypothesized that the pathologic brain dynamics of epileptic seizures are an emergent property of microscale neuronal networks collectively driving the brain away from criticality. Demonstrating this would provide a unifying mechanism linking microscale spatiotemporal activity with emergent brain dysfunction during seizures. Here, we investigated the effect of drug-induced seizures on critical avalanche dynamics, usingin vivowhole-brain two-photon imaging of GCaMP6s larval zebrafish (males and females) at single neuron resolution. We demonstrate that single neuron activity across the whole brain exhibits a loss of critical statistics during seizures, suggesting that microscale activity collectively drives macroscale dynamics away from criticality. We also construct spiking network models at the scale of the larval zebrafish brain, to demonstrate that only densely connected networks can drive brain-wide seizure dynamics away from criticality. Importantly, such dense networks also disrupt the optimal computational capacities of critical networks, leading to chaotic dynamics, impaired network response properties and sticky states, thus helping to explain functional impairments during seizures. This study bridges the gap between microscale neuronal activity and emergent macroscale dynamics and cognitive dysfunction during seizures. SIGNIFICANCE STATEMENTEpileptic seizures are debilitating and impair normal brain function. It is unclear how the coordinated behavior of neurons collectively impairs brain function during seizures. To investigate this we perform fluorescence microscopy in larval zebrafish, which allows for the recording of whole-brain activity at single-neuron resolution. Using techniques from physics, we show that neuronal activity during seizures drives the brain away from criticality, a regime that enables both high and low activity states, into an inflexible regime that drives high activity states. Importantly, this change is caused by more connections in the network, which we show disrupts the ability of the brain to respond appropriately to its environment. Therefore, we identify key neuronal network mechanisms driving seizures and concurrent cognitive dysfunction.
more »
« less
Age-related changes of whole-brain dynamics in spontaneous neuronal coactivations
Abstract Human brains experience whole-brain anatomic and functional changes throughout the lifespan. Age-related whole-brain network changes have been studied with functional magnetic resonance imaging (fMRI) to determine their low-frequency spatial and temporal characteristics. However, little is known about age-related changes in whole-brain fast dynamics at the scale of neuronal events. The present study investigated age-related whole-brain dynamics in resting-state electroencephalography (EEG) signals from 73 healthy participants from 6 to 65 years old via characterizing transient neuronal coactivations at a resolution of tens of milliseconds. These uncovered transient patterns suggest fluctuating brain states at different energy levels of global activations. Our results indicate that with increasing age, shorter lifetimes and more occurrences were observed in the brain states that show the global high activations and more consecutive visits to the global highest-activation brain state. There were also reduced transitional steps during consecutive visits to the global lowest-activation brain state. These age-related effects suggest reduced stability and increased fluctuations when visiting high-energy brain states and with a bias toward staying low-energy brain states. These age-related whole-brain dynamics changes are further supported by changes observed in classic alpha and beta power, suggesting its promising applications in examining the effect of normal healthy brain aging, brain development, and brain disease.
more »
« less
- Award ID(s):
- 2132182
- PAR ID:
- 10369070
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Scientific Reports
- Volume:
- 12
- Issue:
- 1
- ISSN:
- 2045-2322
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract White matter structural connections are likely to support flow of functional activation or functional connectivity. While the relationship between structural and functional connectivity profiles, here called SC-FC coupling, has been studied on a whole-brain, global level, few studies have investigated this relationship at a regional scale. Here we quantify regional SC-FC coupling in healthy young adults using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project and study how SC-FC coupling may be heritable and varies between individuals. We show that regional SC-FC coupling strength varies widely across brain regions, but was strongest in highly structurally connected visual and subcortical areas. We also show interindividual regional differences based on age, sex and composite cognitive scores, and that SC-FC coupling was highly heritable within certain networks. These results suggest regional structure-function coupling is an idiosyncratic feature of brain organisation that may be influenced by genetic factors.more » « less
-
Abstract Impaired cerebrovascular function contributes to the genesis of age‐related cognitive decline. In this study, the hypothesis is tested that impairments in neurovascular coupling (NVC) responses and brain network function predict cognitive dysfunction in older adults. Cerebromicrovascular and working memory function of healthy young (n= 21, 33.2±7.0 years) and aged (n= 30, 75.9±6.9 years) participants are assessed. To determine NVC responses and functional connectivity (FC) during a working memory (n‐back) paradigm, oxy‐ and deoxyhemoglobin concentration changes from the frontal cortex using functional near‐infrared spectroscopy are recorded. NVC responses are significantly impaired during the 2‐back task in aged participants, while the frontal networks are characterized by higher local and global connection strength, and dynamic FC (p< 0.05). Both impaired NVC and increased FC correlate with age‐related decline in accuracy during the 2‐back task. These findings suggest that task‐related brain states in older adults require stronger functional connections to compensate for the attenuated NVC responses associated with working memory load.more » « less
-
Abstract The brain is organized into intrinsically connected functional networks that can be reliably identified during resting-state functional magnetic resonance imaging (fMRI). Healthy aging is marked by decreased network segregation, which is linked to worse cognitive functioning, but aging-related changes in emotion are less well characterized. Valence bias, which represents the tendency to interpret emotionally ambiguous information as positive or negative, is more positive in older than younger adults and is associated with differences in task-based fMRI activation in the amygdala, prefrontal cortex, and a cingulo-opercular (CO) network. Here, we examined valence bias, age, and resting-state network segregation of 12 brain networks in a sample of 221 healthy individuals from 6 to 80 years old. Resting-state network segregation decreased linearly with increasing age, extending prior reports of de-differentiation across the lifespan. Critically, a more positive valence bias was related to lower segregation of the default mode network (DMN), due to stronger functional connectivity of the DMN with CO and, to a lesser extent, the ventral attention network (VAN) in all participants. In contrast to this overall segregation effect, in participants over 39 years old (who tend to show a positive valence bias), bias was also related to weaker connectivity between the DMN and Reward networks. The present findings indicate that specific interactions between the DMN, a task control network (CO), an emotion processing network (Reward), and, to a weaker extent, an attention network (VAN), support a more positive valence bias, perhaps through regulatory control of self-referential processing and reduced emotional reactivity in aging. The current work offers further insight into the functional brain network alterations that may contribute to affective well-being and dysfunction across the lifespan.more » « less
-
Cognition and attention arise from the adaptive coordination of neural systems in response to external and internal demands. The low-dimensional latent subspace that underlies large-scale neural dynamics and the relationships of these dynamics to cognitive and attentional states, however, are unknown. We conducted functional magnetic resonance imaging as human participants performed attention tasks, watched comedy sitcom episodes and an educational documentary, and rested. Whole-brain dynamics traversed a common set of latent states that spanned canonical gradients of functional brain organization, with global desynchronization among functional networks modulating state transitions. Neural state dynamics were synchronized across people during engaging movie watching and aligned to narrative event structures. Neural state dynamics reflected attention fluctuations such that different states indicated engaged attention in task and naturalistic contexts, whereas a common state indicated attention lapses in both contexts. Together, these results demonstrate that traversals along large-scale gradients of human brain organization reflect cognitive and attentional dynamics.more » « less
