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Article ; Online: Using Positron Emission Tomography in Revealing the Mystery of General Anesthesia: Study Design Challenges and Opportunities.

Scheinin, Harry / Alkire, Emilee C / Scheinin, Annalotta / Alkire, Michael T / Kantonen, Oskari / Långsjö, Jaakko

2018 Volume 603, Page(s) 279–303

Abstract: Functional neuroimaging with positron emission tomography (PET) is one of the cornerstones for studying the central nervous system effects of general anesthetics and anesthesia mechanisms. General anesthesia offers a unique and safe way to directly ... ...

Abstract	Functional neuroimaging with positron emission tomography (PET) is one of the cornerstones for studying the central nervous system effects of general anesthetics and anesthesia mechanisms. General anesthesia offers a unique and safe way to directly manipulate consciousness, and can thus be used as a powerful research tool to study the neurobiology of human consciousness. In this chapter, we will address the possibilities of PET imaging in revealing the mysteries of general anesthesia and anesthetic induced unconsciousness and summarize some of the recent advancements in the field. Importantly, we will discuss possible ways to separate brain activity changes associated with the changing level of consciousness from the concentration or dose-dependent direct or indirect drug effects on the brain. We will try to demonstrate how state-of-the-art clinical pharmacology, use of specific anesthetic drugs, and innovative study design solutions could be utilized.
MeSH term(s)	Anesthesia, General/methods ; Anesthetics, Inhalation/pharmacology ; Anesthetics, Intravenous/pharmacology ; Brain/anatomy & histology ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/physiology ; Cerebrovascular Circulation/drug effects ; Cerebrovascular Circulation/physiology ; Consciousness/drug effects ; Consciousness/physiology ; Dose-Response Relationship, Drug ; Functional Neuroimaging/instrumentation ; Functional Neuroimaging/methods ; Glucose/metabolism ; Halothane/pharmacology ; Humans ; Hypnotics and Sedatives/pharmacology ; Lorazepam/pharmacology ; Magnetic Resonance Imaging/methods ; Positron-Emission Tomography/methods ; Propofol/pharmacology ; Research Design ; Wakefulness/drug effects ; Wakefulness/physiology
Chemical Substances	Anesthetics, Inhalation ; Anesthetics, Intravenous ; Hypnotics and Sedatives ; Glucose (IY9XDZ35W2) ; Lorazepam (O26FZP769L) ; Halothane (UQT9G45D1P) ; Propofol (YI7VU623SF)
Language	English
Publishing date	2018-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988 ; 0076-6879
ISSN (online)	1557-7988
ISSN	0076-6879
DOI	10.1016/bs.mie.2018.01.025
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Loss of effective connectivity during general anesthesia.

Alkire, Michael T

International anesthesiology clinics

2008 Volume 46, Issue 3, Page(s) 55–73

MeSH term(s)	Anesthesia, General ; Anesthetics/pharmacology ; Animals ; Brain/blood supply ; Brain/drug effects ; Brain/metabolism ; Consciousness/drug effects ; Cortical Synchronization/drug effects ; Electroencephalography ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Neural Pathways/drug effects ; Synaptic Transmission/drug effects ; Tomography, Emission-Computed ; Unconsciousness/chemically induced
Chemical Substances	Anesthetics
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	210757-0
ISSN	1537-1913 ; 0020-5907
ISSN (online)	1537-1913
ISSN	0020-5907
DOI	10.1097/AIA.0b013e3181755dc6
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Article ; Online: Consciousness, anesthesia, and the thalamocortical system.

Mashour, George A / Alkire, Michael T

Anesthesiology

2013 Volume 118, Issue 1, Page(s) 13–15

MeSH term(s)	Anesthetics, Intravenous/pharmacology ; Deep Sedation/methods ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Propofol/pharmacology ; Thalamic Nuclei/drug effects
Chemical Substances	Anesthetics, Intravenous ; Propofol (YI7VU623SF)
Language	English
Publishing date	2013-01
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	269-0
ISSN	1528-1175 ; 0003-3022
ISSN (online)	1528-1175
ISSN	0003-3022
DOI	10.1097/ALN.0b013e318277a9c6
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Article ; Online: Evolution of consciousness: phylogeny, ontogeny, and emergence from general anesthesia.

Mashour, George A / Alkire, Michael T

Proceedings of the National Academy of Sciences of the United States of America

2013 Volume 110 Suppl 2, Page(s) 10357–10364

Abstract: Are animals conscious? If so, when did consciousness evolve? We address these long-standing and essential questions using a modern neuroscientific approach that draws on diverse fields such as consciousness studies, evolutionary neurobiology, animal ... ...

Abstract	Are animals conscious? If so, when did consciousness evolve? We address these long-standing and essential questions using a modern neuroscientific approach that draws on diverse fields such as consciousness studies, evolutionary neurobiology, animal psychology, and anesthesiology. We propose that the stepwise emergence from general anesthesia can serve as a reproducible model to study the evolution of consciousness across various species and use current data from anesthesiology to shed light on the phylogeny of consciousness. Ultimately, we conclude that the neurobiological structure of the vertebrate central nervous system is evolutionarily ancient and highly conserved across species and that the basic neurophysiologic mechanisms supporting consciousness in humans are found at the earliest points of vertebrate brain evolution. Thus, in agreement with Darwin's insight and the recent "Cambridge Declaration on Consciousness in Non-Human Animals," a review of modern scientific data suggests that the differences between species in terms of the ability to experience the world is one of degree and not kind.
MeSH term(s)	Anesthesia, General ; Animals ; Biological Evolution ; Consciousness/physiology ; Humans ; Models, Biological ; Species Specificity
Language	English
Publishing date	2013-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1301188110
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Article ; Online: Race and Ethnicity in Otolaryngology Academic Publications.

Lindeborg, Michael / Din, Taseer / Araya-Quezada, Cristóbal / Lawal, Sabreena / Heer, Baveena / Rajaguru, Praveen / Joseph, Myriam / Alkire, Blake / Fagan, Johannes

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

2022 Volume 166, Issue 6, Page(s) 1196–1203

Abstract: Objective: Within otolaryngology, race is commonly included as a study covariate; however, its value in clinical practice is unclear. This study sought to explore how race and ethnicity have been used and applied over time in otolaryngology publications. ...

Abstract	Objective: Within otolaryngology, race is commonly included as a study covariate; however, its value in clinical practice is unclear. This study sought to explore how race and ethnicity have been used and applied over time in otolaryngology publications. Data sources: PubMed database. Review methods: A systematic review was done to identify original otolaryngology studies between January 1, 1946, and June 25, 2020, with the following search terms: "otolaryngology" AND "race" OR "ethnicity." Results: Of the 1984 yielded studies, 932 were included in the final analysis. Only 2 studies (0.2%) defined race, and 172 (18.5%) gave participants the opportunity to self-identify race. Less than half (n = 322, 43.8%) of studies controlled for confounders. One hundred studies (10.7%) linked race to genetic factors. An overall 564 (60.5%) made conclusions about race, and 232 (24.9%) mentioned that race is relevant for clinical decision making. The majority of studies had first and senior authors from high-income countries (93.9% and 93.8%, respectively). Over time, there was a significant increase in publications that controlled for confounders, the number of race categories used, and studies that highlighted disparities. Conclusion: Race and ethnicity are often poorly defined in otolaryngology publications. Furthermore, publications do not always control for confounding variables or allow participants to self-identify race. On the basis of our findings, we suggest 7 foundational principles that can be used to promote equitable research in otolaryngology publications. Future efforts should focus on incorporating research guidelines for race and ethnicity into journal publication standards.
MeSH term(s)	Databases, Factual ; Ethnicity ; Humans ; Otolaryngology
Language	English
Publishing date	2022-03-08
Publishing country	England
Document type	Journal Article ; Systematic Review
ZDB-ID	392085-9
ISSN	1097-6817 ; 0161-6439 ; 0194-5998
ISSN (online)	1097-6817
ISSN	0161-6439 ; 0194-5998
DOI	10.1177/01945998221084201
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Article: Functional brain imaging: some parameters for success.

Alkire, Michael T

Anesthesiology

2004 Volume 101, Issue 4, Page(s) 817–819

MeSH term(s)	Brain/physiology ; Humans ; Magnetic Resonance Imaging ; Pain/diagnosis ; Pain/physiopathology
Language	English
Publishing date	2004-07-14
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	269-0
ISSN	0003-3022
ISSN	0003-3022
DOI	10.1097/00000542-200410000-00003
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Article ; Online: Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine.

Kantonen, Oskari / Laaksonen, Lauri / Alkire, Michael / Scheinin, Annalotta / Långsjö, Jaakko / Kallionpää, Roosa E / Kaisti, Kaike / Radek, Linda / Johansson, Jarkko / Laitio, Timo / Maksimow, Anu / Scheinin, Joonas / Nyman, Mikko / Scheinin, Mika / Solin, Olof / Vahlberg, Tero / Revonsuo, Antti / Valli, Katja / Scheinin, Harry

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 26, Page(s) 4884–4895

Abstract: Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain ... ...

Abstract	Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml;
MeSH term(s)	Male ; Humans ; Propofol/pharmacology ; Sevoflurane/pharmacology ; Ketamine/pharmacology ; Dexmedetomidine/pharmacology ; Anesthetics, Inhalation/pharmacology ; Anesthesia ; Anesthetics, Intravenous
Chemical Substances	Propofol (YI7VU623SF) ; Sevoflurane (38LVP0K73A) ; Ketamine (690G0D6V8H) ; Dexmedetomidine (67VB76HONO) ; Anesthetics, Inhalation ; Anesthetics, Intravenous
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2339-22.2023
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Article ; Online: Hypothesis: suppression of memory protein formation underlies anesthetic-induced amnesia.

Alkire, Michael T / Guzowski, John F

Anesthesiology

2008 Volume 109, Issue 5, Page(s) 768–770

MeSH term(s)	Amnesia/chemically induced ; Amnesia/metabolism ; Anesthetics/adverse effects ; Anesthetics/pharmacology ; Animals ; Humans ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/biosynthesis ; Memory/drug effects ; Memory/physiology ; Protein Synthesis Inhibitors/adverse effects ; Protein Synthesis Inhibitors/pharmacology
Chemical Substances	Anesthetics ; Membrane Proteins ; Protein Synthesis Inhibitors
Language	English
Publishing date	2008-11
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	269-0
ISSN	1528-1175 ; 0003-3022
ISSN (online)	1528-1175
ISSN	0003-3022
DOI	10.1097/ALN.0b013e31818aa6f2
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Article: General anesthesia and the neural correlates of consciousness.

Alkire, Michael T / Miller, Jason

Progress in brain research

2005 Volume 150, Page(s) 229–244

Abstract: The neural correlates of consciousness must be identified, but how? Anesthetics can be used as tools to dissect the nervous system. Anesthetics not only allow for the experimental investigation into the conscious-unconscious state transition, but they ... ...

Abstract	The neural correlates of consciousness must be identified, but how? Anesthetics can be used as tools to dissect the nervous system. Anesthetics not only allow for the experimental investigation into the conscious-unconscious state transition, but they can also be titrated to subanesthetic doses in order to affect selected components of consciousness such as memory, attention, pain processing, or emotion. A number of basic neuroimaging examinations of various anesthetic agents have now been completed. A common pattern of regional activity suppression is emerging for which the thalamus is identified as a key target of anesthetic effects on consciousness. It has been proposed that a neuronal hyperpolarization block at the level of the thalamus, or thalamocortical and corticocortical reverberant loops, could contribute to anesthetic-induced unconsciousness. However, all anesthetics do not suppress global cerebral metabolism and cause a regionally specific effect on thalamic activity. Ketamine, a so-called dissociative anesthetic agent, increases global cerebral metabolism in humans at doses associated with a loss of consciousness. Nevertheless, it is proposed that those few anesthetics not associated with a global metabolic suppression effect might still have their effects on consciousness mediated at the level of thalamocortical interactions, if such agents scramble the signals associated with normal neuronal network reverberant activity. Functional and effective connectivity are analysis techniques that can be used with neuroimaging to investigate the signal scrambling effects of various anesthetics on network interactions. Whereas network interactions have yet to be investigated with ketamine, a thalamocortical and corticocortical disconnection effect during unconsciousness has been found for both suppressive anesthetic agents and for patients who are in the persistent vegetative state. Furthermore, recovery from a vegetative state is associated with a reconnection of functional connectivity. Taken together these intriguing observations offer strong empirical support that the thalamus and thalamocortical reverberant network loop interactions are at the heart of the neurobiology of consciousness.
MeSH term(s)	Anesthesia, General ; Brain/physiology ; Consciousness/physiology ; Humans ; Thalamus/physiology
Language	English
Publishing date	2005
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	0079-6123
ISSN	0079-6123
DOI	10.1016/S0079-6123(05)50017-7
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Article: Does the amygdala mediate anesthetic-induced amnesia? Basolateral amygdala lesions block sevoflurane-induced amnesia.

Alkire, Michael T / Nathan, Sheila V

Anesthesiology

2005 Volume 102, Issue 4, Page(s) 754–760

Abstract: Background: Amnesia for aversive events caused by benzodiazepines or propofol depends on the basolateral amygdala (BLA). Whether the amnesia of volatile anesthesia is also mediated through the BLA is unknown. If so, a general principle of anesthetic- ... ...

Abstract	Background: Amnesia for aversive events caused by benzodiazepines or propofol depends on the basolateral amygdala (BLA). Whether the amnesia of volatile anesthesia is also mediated through the BLA is unknown. If so, a general principle of anesthetic-induced amnesia may be emerging. Here, using an inhibitory avoidance paradigm, the authors determine whether BLA lesions prevent sevoflurane-induced amnesia. Methods: Male Sprague-Dawley rats were separated into two groups: sham-operated controls (n = 22) and rats given bilateral N-methyl-D-aspartate lesions of the BLA (n = 32). After a 1-week recovery, the rats were randomly assigned to be trained during either air or sevoflurane (0.3% inspired, 0.14 minimum alveolar concentration) exposure. Animals learned to remain in the starting safe compartment of a step-through inhibitory avoidance apparatus for 100 consecutive seconds by administering foot shock (0.3 mA) whenever they entered an adjacent shock compartment. Memory was assessed at 24 h. Longer latencies to enter the shock compartment at 24 h imply better memory. Results: Sham-air (n = 10) animals had a robust memory, with a median retention latency of 507 s (interquartile range, 270-600 s). Sham-sevoflurane (n = 6) animals were amnesic, with a latency of 52 s (27-120 s) (P < 0.01, vs. sham-air). Both the air-exposed (n = 5) and the sevoflurane-exposed (n = 8) animals with BLA lesions showed robust memory, with latencies of 350 s (300-590 s) and 378 s (363-488 s), respectively. The latencies for both did not differ from the performance of the sham-air group and were significantly greater than the latency of the sham-sevoflurane group (both P < 0.01). Conclusions: BLA lesions block sevoflurane-induced amnesia. A role for the BLA in mediating anesthetic-induced amnesia may be a general principle of anesthetic action.
MeSH term(s)	Amnesia/chemically induced ; Amnesia/psychology ; Amygdala/physiology ; Anesthetics, Inhalation/pharmacology ; Animals ; Learning/drug effects ; Male ; Memory/drug effects ; Methyl Ethers/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sevoflurane
Chemical Substances	Anesthetics, Inhalation ; Methyl Ethers ; Sevoflurane (38LVP0K73A)
Language	English
Publishing date	2005-03-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	269-0
ISSN	0003-3022
ISSN	0003-3022
DOI	10.1097/00000542-200504000-00010
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