How do neurons communicate and how is their communication altered when consciousness is suppressed by anesthetics? Is there a difference in the anesthetic effect on neuronal communication over long-distances versus local circuits? How is communication restored when subjects regain consciousness? What are the critical neuronal changes necessary to restore consciousness? These are paramount questions that aid the understanding of the neuronal basis of consciousness.

Our lab was probably the first to investigate the dose-dependent effect of modern, clinically used anesthetics on cortical multineuronal activity in chronically instrumented, freely moving animals using high-density microelectrode arrays. Former experiments mostly utilized individual epidural or intracortical electrodes to measure local field potentials or multiunit activity. These methods have now been replaced by high-density microelectrode and optrode recording and stimulation.

 

The hypothesis of large-scale integration.

There is little doubt today that neuronal activity that instantiates human and animal cognition involves the integrative function of a network of brain regions, particularly those that consist of large-scale cortical and subcortical circuits. Based on specific, precisely controlled molecular, synaptic, and local circuit operations, the final integration of neuronal information into perceptual, volitional, and mental acts presumably occurs in these large-scale circuits. A plausible hypothesis is that a final common cause of a change in state of consciousness during anesthesia or natural sleep is in the spatiotemporal domain of large-scale integration in the brain.

 

 

 

Publications

Hudetz AG, Mashour GA: Disconnecting Consciousness: Is There a Common Anesthetic End Point? Anesth Analg. 2016 Nov;123(5):1228-1240. PubMed PMID: 27331780; PMCID: PMC5073005.

Mashour GA, Hudetz AG: Bottom-Up and Top-Down Mechanisms of General Anesthetics Modulate Different Dimensions of Consciousness. Front. Neural Circuits 2017 Jun 20;11:44. doi: 10.3389/fncir.2017.00044. eCollection 2017. PMID: 28676745

The feedback hypothesis.

A well-established effect of anesthetics on large-scale networks of the brain is that they preferentially suppress information transfer in the cerebral cortex in the anterior-posterior direction. This was first observed during the administration of various types of volatile (inhalational) anesthetics in a rat model where local field potentials were measured at multiple sites in the cortex.  The effect has been confirmed by numerous human EEG and fMRI investigations with multiple types of anesthetics and has become the cornerstone of a current theory of anesthetic-induced unconsciousness.  This theory is further supported by the observation that anesthetics selectively suppress long-latency evoked responses that are thought to arise from recurrent (e.g. anterior-posterior) feedback.

 

Our current research is directed to answering the questions how feedforward and feedback interactions change dynamically during various levels of anesthesia (and levels of consciousness), if there are specific, recurrent circuits that are more affected than others, and if they have a causal role for influencing consciousness.

 

 

 

Publications

Imas OA, Ropella KM, Ward BD, Wood JD, Hudetz AG. Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat. Neurosci Lett. 2005;387(3):145-50. PubMed PMID: 16019145.

Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia. Science. 2008;322(5903):876-80. PubMed PMID: 18988836; PMCID: 2743249.

Hudetz AG: Cortical Disintegration Mechanism of Anesthetic-Induced Unconsciousness. Suppressing The Mind: Anesthetic Modulation of Memory and Consciousness, Humana Press, pp 99-125, 2010.