Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness
Abstract
Understanding the neural basis of consciousness is fundamental to neuroscience research. Disruptions in cortico-cortical connectivity have been suggested as a primary mechanism of unconsciousness. By using a novel combination of positron emission tomography and functional magnetic resonance imaging, we studied anesthesia-induced unconsciousness and recovery using the α2-agonist dexmedetomidine. During unconsciousness, cerebral metabolic rate of glucose and cerebral blood flow were preferentially decreased in the thalamus, the Default Mode Network (DMN), and the bilateral Frontoparietal Networks (FPNs). Cortico-cortical functional connectivity within the DMN and FPNs was preserved. However, DMN thalamo-cortical functional connectivity was disrupted. Recovery from this state was associated with sustained reduction in cerebral blood flow, and restored DMN thalamo-cortical functional connectivity. We report that loss of thalamo-cortical functional connectivity is sufficient to produce unconsciousness.
Article and author information
Author details
Ethics
Human subjects: The Human Research Committee and the Radioactive Drug Research Committee at the Massachusetts General Hospital approved the study protocol. After an initial email/phone screen, potential study subjects were invited to participate in a screening visit. At the screening visit, informed consent including the consent to publish was requested after the nature and possible consequences of the study was explained. All subjects provided informed consent and were American Society of Anesthesiology Physical Status I with Mallampati Class I airway anatomy.
Copyright
© 2014, Akeju et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,519
- views
-
- 690
- downloads
-
- 140
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Axonal and dendritic recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Experimentally-based detailed biophysical models have shown that the key factor responsible for the accelerated EPSP propagation in human cortical dendrites is the large conductance load imposed at the soma by the large basal dendritic tree. Additionally, larger dendritic diameters and differences in cable and ion channel properties in humans contribute to enhanced signal propagation. Our integrative experimental and modeling study provides new insights into the scaling rules that help maintain information processing speed albeit the large and sparse neurons in the human cortex.
-
- Neuroscience
When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.