Richard J. Haier

Cortical glucose metabolic rate correlates of abstract reasoning and attention studied with positron emission tomography

Abstract Three groups of young, healthy males underwent positron emission tomography of the head, using 18fluoro-2-deoxyglucose as the uptake tracer. During the uptake, one group (n = 8) did an abstract reasoning test (Ravens Advanced Progressive Matrices [RAPM]); another (n = 13) performed a visual vigilance task (Continuous Performance Test [CPT] task); and the other (n = 9) simply watched flashing visual stimuli (CPT no task). ANOVA revealed that both the RAPM and the CPT groups activated the right hemisphere. A priori and exploratory t-tests indicated some left-hemisphere areas of activation for the RAPM, especially posterior cortex. Performance on the RAPM showed significant negative correlations with cortical metabolic rates. CPT performace showed few significant correlations with cortical metabolic rate. Although this study does not strongly implicate any one brain region in performance of the RAPM or CPT task, the inverse glucose/RAPM performance correlations suggest that some individual differences in cognitive ability may be related to efficiency or density of neutral circuits.

Structural brain variation and general intelligence

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 (N = 47; P < 0.05 corrected for multiple comparisons), more gray matter is associated with higher IQ in discrete Brodmann areas (BA) including frontal (BA 10, 46, 9), temporal (BA 21, 37, 22, 42), parietal (BA 43 and 3), and occipital (BA 19) lobes and near BA 39 for white matter (WM). These results underscore the distributed neural basis of intelligence and suggest a developmental course for volume--IQ relationships in adulthood.

Regional glucose metabolic changes after learning a complex visuospatial/motor task: A positron emission tomographic study.

Regional cerebral glucose metabolic rate (GMR) quantified with positron emission tomography (PET) with 18-fluoro-2-deoxyglucose (FDG) was measured twice in 8 young men performing a complex visuospatial/motor task (the computer game Tetris), before and after practice. After 4-8 weeks of daily practice on Tetris, GMR in cortical surface regions decreased despite a more than 7-fold increase in performance. Subjects who improved their Tetris performance the most after practice showed the largest glucose metabolic decreases after practice in several areas. These results suggest that learning may result in decreased use of extraneous or inefficient brain areas. Changes in regional subcortical glucose metabolic rate with practice may reflect changes in cognitive strategy that are a part of the learning process.

Toward a Unified Theory of Narcosis: Brain Imaging Evidence for a Thalamocortical Switch as the Neurophysiologic Basis of Anesthetic-Induced Unconsciousness

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 different commonly used volatile agents. These findings are discussed in relation to findings from sleep neurophysiology and the implications of this work for consciousness research. It is hypothesized that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is, as with sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. A model of anesthetic-induced unconsciousness is introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system, thus providing for a unitary physiologic theory of narcosis related to consciousness.

Cerebral Metabolism during Propofol Anesthesia in Humans Studied with Positron Emission Tomography

BACKGROUND 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. METHODS Six volunteers each underwent two PET scans; one scan assessed awake-baseline metabolism, and the other assessed metabolism during anesthesia with a propofol infusion titrated to the point of unresponsiveness (mean rate +/- SD = 7.8 +/- 1.5 mg.kg-1.h-1). Scans were obtained using the 18fluorodeoxyglucose technique. RESULTS Awake whole-brain glucose metabolic rates (GMR) averaged 29 +/- 8 mumoles.100 g-1.min-1 (mean +/- SD). Anesthetized whole-brain GMR averaged 13 +/- 4 mumoles.100 g-1.min-1 (paired t test, P < or = 0.007). GMR decreased in all measured areas during anesthesia. However, the decrease in GMR was not uniform. Cortical metabolism was depressed 58%, whereas subcortical metabolism was depressed 48% (P < or = 0.001). Marked differences within cortical regions also occurred. In the medial and subcortical regions, the largest percent decreases occurred in the left anterior cingulate and the inferior colliculus. CONCLUSION Propofol produced a global metabolic depression on the human central nervous system. The metabolic pattern evident during anesthesia was reproducible and differed from that seen in the awake condition. These findings are consistent with those from previous animal studies and suggest PET may be useful for investigating the mechanisms of anesthesia in humans.

Intelligence and changes in regional cerebral glucose metabolic rate following learning

Abstract Positron emission tomography (PET) studies of brain glucose metabolic rate (GMR) in normal volunteers report inverse correlations between GMR and scores on the Ravens Advanced Progressive Matrices (RAPM) and verbal fluency. A new study in eight normal men reports widespread significant GMR decreases following learning a complex task (the computer game “Tetris”). The purpose of this study is to ascertain the correlations between GMR changes following learning “Tetris” and psychometric intelligence scores (RAPM and WAIS-R) to determine whether high-ability subjects show the largest GMR decreases, as predicted by a brain efficiency hypothesis. This hypothesis is supported with significant correlations between the magnitude of GMR change and intelligence scores in many brain areas that changed with learning. Some implications for the role of attention, memory, and speed of processing are discussed in view of the specific brain areas involved.

The neuroanatomy of general intelligence: sex matters

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 parietal lobes (BA 8, 9, 39, 40), whereas the strongest correlations in women are in the frontal lobe (BA10) along with Brocas area. Men and women apparently achieve similar IQ results with different brain regions, suggesting that there is no singular underlying neuroanatomical structure to general intelligence and that different types of brain designs may manifest equivalent intellectual performance.

Functional Brain Imaging during Anesthesia in Humans Effects of Halothane on Global and Regional Cerebral Glucose Metabolism

BACKGROUND 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 halothanes in vivo cerebral metabolic effects. METHODS Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.

Positron Emission Tomography Study of Regional Cerebral Metabolism in Humans during Isoflurane Anesthesia

Background 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 human cerebral glucose metabolism using positron emission tomography (PET). Methods Five volunteers each underwent two PET scans; one scan assessed awake‐baseline metabolism and the other scan assessed metabolism during isoflurane anesthesia titrated to the point of unresponsiveness (means +/‐ SD; expired = 0.5 +/‐ 0.1%). Scans were obtained with a GE2048 scanner (4.5‐mm resolution‐FWHM) using the18 fluorodeoxyglucose technique. Results Awake whole‐brain glucose metabolism averaged 6.9 +/‐ 1.5 mg [center dot] 100 g sup ‐1 [center dot] min sup ‐1 (means +/‐ SD). Isoflurane reduced whole‐brain metabolism 46 +/‐ 11% to 3.6 +/‐ 0.3 mg [center dot] 100 g sup ‐1 [center dot] min sup ‐1 (P less or equal to 0.005). Regional metabolism decreased fairly uniformly throughout the brain, and no evidence of any regional metabolic increases were found in any brain region for any participant. A region‐of‐interest analysis showed that the pattern of regional metabolism evident during isoflurane anesthesia was not significantly different from that seen when participants were awake. Conclusion These data clarify that the anesthetic state evident in the living human brain during unresponsiveness induced with isoflurane is associated with a global, fairly uniform, whole‐brain glucose metabolic reduction of 46 +/‐ 11%.

Neuroanatomy of creativity

Creativity has long been a construct of interest to philosophers, psychologists and, more recently, neuroscientists. Recent efforts have focused on cognitive processes likely to be important to the manifestation of novelty and usefulness within a given social context. One such cognitive process – divergent thinking – is the process by which one extrapolates many possible answers to an initial stimulus or target data set. We sought to link well established measures of divergent thinking and creative achievement (Creative Achievement Questionnaire – CAQ) to cortical thickness in a cohort of young (23.7 ± 4.2 years), healthy subjects. Three independent judges ranked the creative products of each subject using the consensual assessment technique (Amabile, 1982) from which a “composite creativity index” (CCI) was derived. Structural magnetic resonance imaging was obtained at 1.5 Tesla Siemens scanner. Cortical reconstruction and volumetric segmentation were performed with the FreeSurfer image analysis suite. A region within the lingual gyrus was negatively correlated with CCI; the right posterior cingulate correlated positively with the CCI. For the CAQ, lower left lateral orbitofrontal volume correlated with higher creative achievement; higher cortical thickness was related to higher scores on the CAQ in the right angular gyrus. This is the first study to link cortical thickness measures to psychometric measures of creativity. The distribution of brain regions, associated with both divergent thinking and creative achievement, suggests that cognitive control of information flow among brain areas may be critical to understanding creative cognition. Hum Brain Mapp, 2010.