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Publications
Publications (81)
Introduction:
The highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral meta...
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...
Evidence from the animal literature suggests that post-training glucocorticoids interact with noradrenergic activation at acquisition to enhance memory consolidation for emotional stimuli. While there is evidence that glucocorticoids enhance memory for emotional material in humans, the extent to which this depends on noradrenergic activation at enc...
The molecular targets and neural circuits that underlie general anesthesia are not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker-related) delayed rectifier K(+) channels in the central medial thalamic nucleus (CMT) are important targets for volatile anesthetics. The modulation of Kv1 channels by volatiles is network specif...
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 s...
Background:
Work suggests the amnesia from dexmedetomidine (an α2-adrenergic agonist) is caused by a failure of information to be encoded into long-term memory and that dexmedetomidine might differentially affect memory for emotionally arousing material. We investigated these issues in humans using event-related neuroimaging to reveal alterations...
The impact of synthetic amyloid β (1-42) (Aβ(1-42)) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ(1-4...
One of the greatest challenges of modern neuroscience is to discover the neural mechanisms of consciousness and to explain how they produce the conscious state. We sought the underlying neural substrate of human consciousness by manipulating the level of consciousness in volunteers with anesthetic agents and visualizing the resultant changes in bra...
This resource thoroughly examines the anesthetic modulation of the central, peripheral, and autonomic nervous systems and will help redefine anesthesiology as a fundamentally neuroscientific field. It is organized by sections, with each focusing on a different part of the nervous system. State-of-the-art chapters are written by field leaders in ane...
Neuroimaging the effect of anesthesia in the human brain reveals that anesthesia suppresses the functioning of the brain both
in a global- and regional-specific manner. The suppression of activity generally has a global component to it (i.e., the entire
brain seems to shut down), but on top of that a few select regions appear to be more suppressed...
Consider what it would be like to be without memory. No memory of the past, or of future experiences that will make up the past. No knowledge of your childhood, your school days, your marriage, your children, the lifetime of facts you have learned, the history of your country, the names of important people and places, and so on. It would be as if y...
The Drosophila Shaker mutant fruit-fly, with its malfunctioning voltage-gated potassium channel, exhibits anesthetic requirements that are more than twice normal. Shaker mutants with an abnormal Kv1.2 channel also demonstrate significantly reduced sleep. Given the important role the thalamus plays in both sleep and arousal, the authors investigated...
When we are anesthetized, we expect consciousness to vanish. But does it always? Although anesthesia undoubtedly induces unresponsiveness
and amnesia, the extent to which it causes unconsciousness is harder to establish. For instance, certain anesthetics act on
areas of the brain's cortex near the midline and abolish behavioral responsiveness, but...
In 1947, a second power of anesthesia was described: "With anesthetic agents we seem to have a tool for producing and holding at will, and at little risk, different levels of consciousness--a tool that promises to be of great help in studies of mental phenomena." In 1995, anesthetic manipulation was coupled with neuroimaging, paving the way for det...
It is hypothesized that emotional arousal modulates long-term memory consolidation through the amygdala. Gaseous anesthetic agents are among the most potent drugs that cause temporary amnesia, yet the effects of inhalational anesthesia on human emotional memory processing remain unknown. To study this, two experiments were performed with the common...
Neuronal nicotinic acetylcholine receptors are both potently inhibited by anesthetics and densely expressed in the thalamus. Brain imaging shows that thalamic activity suppression accompanies anesthetic-induced unconsciousness. Therefore, anesthetic-induced unconsciousness may involve direct antagonism of thalamic nicotinic receptors. The authors t...
Background: Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought. Methods: First, the memory-enhancing potential of various an...
Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought.
First, the memory-enhancing potential of various anesthetics was determi...
Response time (RT) generally slows with aging, but the contribution of structural brain changes to this slowing is unknown. We used voxel-based morphometry (VBM) to determine gray matter (GM) and white matter (WM) brain volumes in 9 middle-aged adults (38-58 years old) and 9 seniors (66-82 years old). We correlated brain volumes with RT assessed in...
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...
We examined the relationship between structural brain variation and general intelligence using voxel-based morphometric analysis of MRI data in men and women with equivalent IQ scores. Compared to men, women show more white matter and fewer gray matter areas related to intelligence. In men IQ/gray matter correlations are strongest in frontal and pa...
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 consciousnes...
Total brain volume accounts for about 16% of the variance in general intelligence scores (IQ), but how volumes of specific regions-of-interest (ROIs) relate to IQ is not known. We used voxel-based morphometry (VBM) in two independent samples to identify substantial gray matter (GM) correlates of IQ. Based on statistical conjunction of both samples...
Doses of volatile anesthetics around 0.3 minimum alveolar concentration (MAC) inhibit learning. However, threshold amnesic doses and relative potencies between agents are not well established. The authors determined amnesic potency in rats for four common volatiles and nitrous oxide.
After institutional review board approval, adult Sprague-Dawley r...
The amygdala appears necessary for enhanced long-term memory associated with emotionally arousing events. Recent brain imaging investigations support this view and indicate a sex-related hemispheric lateralization exists in the amygdala relationship to memory for emotional material. This study confirms and further explores this finding. Healthy men...
To elucidate neural correlates associated with processing of tonic aching pain, the authors used high-field (3-T) functional magnetic resonance imaging with a blocked parametric study design and characterized regional brain responses to electrical stimulation according to stimulus intensity-response functions.
Pain was induced in six male volunteer...
Adults with Down syndrome (DS) are at increased risk for dementia and provide an opportunity to identify patterns of brain activity that may precede dementia. Studies of early Alzheimer's disease (AD) and risk of AD show decreased function in posterior cingulate and temporal cortex as initial indicators of the disease process, but whether the origi...
Brain imaging can help identify the functional neuroanatomy of general intelligence (i.e., “g”) and indicate how brain areas salient to g relate to information processing. An important question is whether individual differences in g among subjects are related to brain function even when nonreasoning tasks are studied. If so, this would imply that i...
Previous structural brain imaging studies of Down Syndrome (DS) have offered important insights into the underlying morphometric aberrations associated with the condition. These previous studies have relied almost exclusively on classic region-of-interest (ROI)-based morphometry, a method in which a finite number of anatomical structures must be de...
Whereas converging lines of evidence suggest that anesthetic-induced unconsciousness may result from disruption of functional interactions within neural networks involving the thalamus and cerebral cortex, the effects anesthetics have on human thalamocortical connectivity remain unexamined with current neuroimaging techniques. To address this issue...
Consciousness is at the very core of the human condition. Yet only in recent decades has it become a major focus in the brain and behavioral sciences. Scientists now know that consciousness involves many levels of brain functioning, from brainstem to cortex. The almost seventy articles in this book reflect the breadth and depth of this burgeoning f...
Abundant evidence indicates that endogenous stress hormones like epinephrine and cortisol modulate memory consolidation in animals. Despite this evidence, there has been no demonstration that endogenous stress hormones modulate memory consolidation in humans. In the present study, healthy subjects viewed a series of 21 slides, and immediately after...
As the unitary theory of anesthesia gives way to the "multiple sites, multiple mechanisms" concept, the sites involved in mediating the components of anesthesia must be identified. In the current study, we test the hypothesis that the basolateral amygdala complex (BLAC) is a brain site involved with mediating propofol-induced amnesia.
Male Sprague-...
The critical role that observation can play in solving scientific problems is illustrated with several examples.
If the in vivo effects of anaesthesia are mediated through a specific receptor system, then a relationship could exist between the regional
changes in brain metabolism caused by a particular agent and the underlying regional distribution of the specific receptors
affected by that agent. Positron emission tomography data from volunteers studied whil...
We tested the possibility suggested by previous imaging studies that amygdala participation in the storage of emotionally influenced memory is differentially lateralized in men and women. Male and female subjects received two PET scans for regional cerebral glucose-one while viewing a series of emotionally provocative (negative) films, and a second...
A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Functional-brain-imaging data obtained from 11 volunteers during general anesthesia showed specific suppression of regional thalamic and midbrain reticular formation activity across two d...
Methods. After institutional approval, sham-operated and NMDA-induced BL amygdala lesioned rats were exposed to either air or 2% inspired halothane for 15 min, followed by a 12 min recovery before training on a continuous multiple-trial inhibitory avoidance task. Rats were placed into the light side of a light/dark "V" channel training box. Upon cr...
Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects.
Five male volunteers each underwe...
Participation of two medial temporal lobe structures, the hippocampal region and the amygdala, in long-term declarative memory encoding was examined by using positron emission tomography of regional cerebral glucose. Positron emission tomography scanning was performed in eight healthy subjects listening passively to a repeated sequence of unrelated...
To help elucidate the relationship between anesthetic-induced changes in the electroencephalogram (EEG) and the concurrent cerebral metabolic changes caused by anesthesia, positron emission tomography data of cerebral metabolism obtained in volunteers during anesthesia were correlated retrospectively with various concurrently measured EEG descripto...
Although the anesthetic effects of the intravenous anesthetic agent propofol have been studied in the living human brain using brain imaging technology, the nature of the anesthetic state evident in the human brain during inhalational anesthesia remains unknown. To examine this issue, the authors studied the effects of isoflurane anesthesia on huma...
glucose metabolic states, can be assessed directly in the living human brain. Also, PET can be used to assess the regional distributions of numerous components of the various neurotransmitter systems. One of the potentially most intriguing possibilities for PET and anesthesia research is that of using PET in brain activation studies where anestheti...
Previous studies of the cortical input to the mammalian dorsal lateral geniculate nucleus (LGN) have identified a number of possible functions for the corticogeniculate pathway, including alteration of LGN spatial frequency selectivity and facilitation of both binocular interactions and orientation selectivity. These changes may be due to either a...
Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting...
One method for investigating the neurobiology of consciousness is to experimentally manipulate consciousness as a variable and then visualize the resultant functional brain changes with advanced imaging techniques. To begin investigation into this area, healthy volunteers underwent positron emission tomography scanning while listening to randomized...
Brain imaging technology combined with anesthesia research demonstrates that two different "depth of Anesthesia" variables show functional neuroanatomic overlap in monitoring cerebral metabolism of the anterior cingulate gyrus and the midbrain reticular formation.
Although the effects of propofol on cerebral metabolism have been studied in animals, these effects have yet to be directly examined in humans. Consequently, we used positron emission tomography (PET) to demonstrate in vivo the regional cerebral metabolic changes that occur in humans during propofol anesthesia.
Six volunteers each underwent two PET...
To clarify the nature of ischemic striatal dopamine release during the earliest periods of neuronal injury, we used chronoamperometry to measure dopamine levels every 60 seconds during various durations of ischemia in 32 gerbils. Catecholamine-selective electrodes were implanted into the brains of anesthetized gerbils subjected to 2, 5, or 10 minut...
Catecholamine (CA) release was measured in vivo in the monkey and cat visual cortices electrochemically. Stereate-modified, graphite-paste electrodes were used to monitor changes in norepinephrine and dopamine release. Micromolar changes in CA concentration were obtained by stimulation of the eye with nonspecific (strobe) or specific (oriented bars...
Participation of two medial temporal lobe structures, the hippocampal region and the amygdala, in long-term declarative memory encoding was examined by using positron emission tomography of regional cerebral glucose. Positron emission tomography scanning was per- formed in eight healthy subjects listening passively to a repeated sequence of unrelat...
