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Ronald A Yeo

Publications and source records attributed to Ronald A Yeo.

16 recordsLinked to original sources

Impairment on the hippocampal-dependent virtual Morris water task in schizophrenia.

Traditional neuropsychological tests of visual and verbal memory have been used to evaluate memory deficits in schizophrenia. However, these tests cannot be used in non-human animal research, which is important for the discovery of treatments that will improve cognition and for study of the etiology of schizophrenia. To help bridge the gap between human and non-human animal research on hippocampal function in schizophrenia, this study sought to characterize the behavioral performance exhibited by patients using the Morris water task (MWT). The MWT has been shown in human and non-human animal studies to be hippocampus-dependent. In the virtual MWT, human subjects navigate a computer-generated on-screen environment to escape from the "water" by locating a platform. Patients with schizophrenia and controls performed two versions of the virtual MWT: a hippocampal-dependent hidden-platform version, relying on allocentric navigational abilities, and a non-hippocampal-dependent visible-platform version, relying on cued-navigational abilities. Patients traveled further and took longer to find the hidden platform over training blocks and spent less time in the correct quadrant during a probe trial. There was no deficit in the visible-platform condition. These findings identify a behavioral impairment on a hippocampal-dependent task in schizophrenia and support using the MWT in testing animal models of schizophrenia.

Adult↗

Developmental instability and the neural dynamics of the speed-intelligence relationship.

Two of the most securely established findings in the biology of intelligence are the relationship between reaction time (RT) and intelligence, and the heritability of intelligence. To investigate why RT may related to intelligence, researchers have used a variety of techniques to subdivide RT into cognitive and motor components. In the current study, magnetoencephalographic (MEG) dipole latencies were used to examine the speed and timing of specific brain processing stages engaged during visually cued simple and choice reaction time tasks. Simple and choice reaction time and timing of MEG sources were considered in relation to fluid intelligence (as measured by the Raven's Advanced Progressive Matrices, RAPM). To address heritability of intelligence, developmental instability (DI) was assessed, measured here as fluctuating asymmetry. DI represents the degree to which an organism is susceptible to developmental stress arising from both environmental and genomic sources. Analyses showed that choice, but not simple reaction time was negatively correlated with RAPM score. MEG revealed a set of complex relationships between the timing of regional brain activations and psychometric intelligence. The neural component associated with integration of sensory and motor information was most associated with RAPM compared to other components. Higher values of fluctuating asymmetry predicted reduced psychometric intelligence, a result suggesting that some part of the variance of the heritability of intelligence reflects DI. Fluctuating asymmetry was significantly and negatively correlated with timing during all components of task completion. These observations suggest that fluid intelligence is primarily related to speed during processing associated with decision time, while fluctuating asymmetry predicted slower processing across all stages of information processing.

Adolescent↗

Magnetic resonance spectroscopy detects brain injury and predicts cognitive functioning in children with brain injuries.

Proton magnetic resonance spectroscopy (1H-MRS) and neuropsychological assessment were utilized in a longitudinal investigation of traumatic brain injury (TBI) in children. A spectroscopic imaging protocol was implemented, and neurometabolite ratios of NAA/Cre and Cho/Cre were calculated for anterior and posterior halves of a supraventricular slab of brain tissue. NAA/Cre was reduced and Cho/Cre increased in TBI patients as compared to controls, for both brain regions. Each ratio predicted aspects of neuropsychological performance, though the specific relationships varied somewhat by region and function. Anterior NAA/Cre increased and anterior Cho/Cre decreased from 3 to 21 weeks post-injury, suggesting neurometabolic recovery.

Adolescent↗

Sex differences in N-acetylaspartate correlates of general intelligence: an 1H-MRS study of normal human brain.

Researchers have long attempted to determine brain correlates of intelligence using available neuroimaging technology including CT, MRI, PET, and fMRI. Although structural and functional imaging techniques are well suited to assess gross cortical regions associated with intelligence, the integrity and functioning of underlying white matter networks critical to coordinated cortical integration remain comparatively understudied. A relatively recent neuroimaging advance is magnetic resonance spectroscopy (MRS) which allows for interrogation of biochemical substrates of brain structure and function in vivo. In this study, we examined twenty-seven normal control subjects (17 male, 10 female) to determine whether N-acetylaspartate (NAA), a metabolite found primarily within neurons, is related to intelligence as assessed by the Wechsler Adult Intelligence Scale-III. Of the three white matter regions studied (i.e., left frontal, right frontal, left occipito-parietal), we found that a model including only left occipito-parietal white matter predicted intellectual performance [F(1,25) = 8.65, P = .007; r2 = .26], providing regional specificity to our previous findings of NAA-IQ relationships. Moreover, we found that a complex combination of left frontal and left occipito-parietal NAA strongly predicted performance in women, but not men [F(2,7) = 21.84, P < .001; adjusted r2 = .82]. Our results highlight a biochemical substrate of normal intellectual performance, mediated by sex, within white matter association fibers linking posterior to frontal brain regions.

Adolescent↗

Virtual navigation in humans: the impact of age, sex, and hormones on place learning.

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20-90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20-39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Adult↗

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 Broca's 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.

Adolescent↗

A specific test of hippocampal deficit in schizophrenia.

Despite numerous studies in which hippocampal abnormalities were found, schizophrenia patients' hippocampal neural activity has not been systematically evaluated on a specific hippocampal-dependent task. The transverse-patterning task (TP) is sensitive to the relational mnemonic capabilities of the hippocampus. Ten schizophrenia patients and 10 controls performed TP and control tasks that are not hippocampal dependent. As predicted, patients displayed a behavioral impairment in TP and not in control tasks. Magnetoencephalography showed controls activating right hippocampus during TP performance. Patients showed more bilateral or left hippocampal activation during TP, and greater left lateralization was associated with better performance on TP. Patients' abnormal hippocampal lateralization may play a role in the hippocampal-dependent behavioral deficit.

Adult↗

Selective cognitive impairments associated with NMDA receptor blockade in humans.

Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) may be involved in the pathophysiology of schizophrenia. NMDAR antagonists like ketamine induce schizophrenia-like features in humans. In rodent studies, NMDAR antagonism impairs learning by disrupting long-term potentiation (LTP) in the hippocampus. This study investigated the effects of ketamine on spatial learning (acquisition) vs retrieval in a virtual Morris water task in humans. Verbal fluency, working memory, and learning and memory of verbal information were also assessed. Healthy human subjects participated in this double-blinded, placebo-controlled study. On two separate occasions, ketamine/placebo was administered and cognitive tasks were assessed in association with behavioral ratings. Ketamine impaired learning of spatial and verbal information but retrieval of information learned prior to drug administration was preserved. Schizophrenia-like symptoms were significantly related to spatial and verbal learning performance. Ketamine did not significantly impair attention, verbal fluency, or verbal working memory task performance. Spatial working memory was slightly impaired. In conclusion, these results provide evidence for ketamine's differential impairment of verbal and spatial learning vs retrieval. By using the Morris water task, which is hippocampal-dependent, this study helps bridge the gap between nonhuman animal and human NMDAR antagonism research. Impaired cognition is a core feature of schizophrenia. A better understanding of NMDA antagonism, its physiological and cognitive consequences, may provide improved models of psychosis and cognitive therapeutics.

Cognition Disorders↗

Structural brain variation, age, and response time.

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 both a simple visual stimulus-response task and a visual continuous recognition memory task. No GM correlations with simple RT were significant; there was one WM correlation in the right fusiform gyrus. In the memory task, faster RT was correlated (p < .05, corrected) with less GM in the globus pallidus, the parahippocampus, and the thalamus for both groups. Several Brodmann areas (BA) differed between the groups such that in each area, less GM was correlated with slower RTs in the middle-aged group but with faster RTs in the senior group (BAs 19, 37, 46, 9, 8, 6, 13, 10, 41, and 7). The results suggest that individual differences in specific brain structure volumes should be considered as potential moderating factors in cognitive brain imaging studies.

Adult↗

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.

Adult↗

Magnetic resonance imaging correlates of attention-deficit/hyperactivity disorder in children.

This study compared magnetic resonance imaging size differences in several brain regions and neurocognitive function in a group of male and female children with attention-deficit/hyperactivity disorder (ADHD) with no comorbid learning disorders with a normal control group of children. The ADHD group demonstrated smaller total brain, superior prefrontal, and right superior prefrontal volumes, as well as significantly smaller areas for cerebellar lobules I-V and VIII-X, total corpus callosum area, and splenium. No group differences were observed for the inferior prefrontal, caudate, or cerebellar volumes, or for the area of cerebellar lobules VI-VII. In the ADHD group but not in the control group, greater right superior prefrontal volume predicted poorer performance on a test of sustained attention. Patterns of brain abnormality did not differ in male and female children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

The aging hippocampus: cognitive, biochemical and structural findings.

Aging is often accompanied by learning and memory problems, many of which resemble deficits associated with hippocampal damage. Studies of aging in nonhuman animals have demonstrated hippocampus-related memory decline, and point to a possible locus for impairments associated with normal and pathological aging in humans. Two well-characterized hippocampus-dependent tasks in nonhuman animal literature are the Morris water task (MWT) and the transverse patterning discrimination task (TPDT). We employed the virtual MWT and the TPDT to assess hippocampus-dependent cognition in humans. Magnetic resonance imaging and proton magnetic resonance spectroscopy were employed to measure hippocampal volume and neurochemistry respectively. Age-related deficits were observed in performance on both hippocampus-dependent tasks. This pattern of impairment was accompanied by decreased hippocampal NAA/Cre ratios and volume, both of which imply neuronal loss and/or decrease in neuronal density. Collectively, our results suggest that hippocampus undergoes structural and biochemical changes with normal aging and that these changes may represent an important component of age-related deterioration in hippocampus-dependent cognition.

Adult↗

Proton magnetic resonance spectroscopy investigation of the right frontal lobe in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To investigate neurometabolite concentrations in right prefrontal white matter in children with attention-deficit/hyperactivity disorder (ADHD) and relations of neurometabolites with attention skill and frontal anatomy. METHOD: Single voxel proton magnetic resonance spectroscopy ( H-MRS), quantitative morphometric analysis of left and right dorsolateral frontal volumes, and assessment of attentional problems with the Conners Continuous Performance Test were undertaken in 23 children (17 male) with ADHD (with no comorbid learning disabilities) and 24 matched controls (16 male). RESULTS: No overall group differences were found for any neurometabolite. However, a group by sex interaction was noted for -acetylaspartate, such that girls with ADHD had especially low concentrations. Morphological analyses revealed smaller right (but not left) dorsolateral volumes in children with ADHD, and in the ADHD group this volume correlated with neurometabolite concentrations. In the ADHD group Continuous Performance Test performance was related to both dorsolateral volume and the creatine-phosphocreatine peak from H-MRS. CONCLUSIONS: These results add to a growing body of evidence suggesting sex-specific neurobiological differences in ADHD and draw attention to relationships between neurochemistry, neuroanatomy, and performance in children with ADHD. Study limitations include small sample size and clinical heterogeneity among the children with ADHD.

Aspartic Acid↗

Biochemical markers of mood: a proton magnetic resonance spectroscopy study of normal human brain.

BACKGROUND: Elevated brain Cho has been shown within the basal ganglia and frontal (i.e., orbitofrontal and cingulate) cortices in patients with mood disorders utilizing Proton Magnetic Resonance Spectroscopy (1H-MRS). We sought to determine the relationship between Cho and mood in a cohort of healthy young subjects. METHODS: Twenty-seven subjects without neurologic or psychiatric disorders were evaluated with the Positive and Negative Affect Scale and underwent 1H-MRS of bilateral frontal and occipito-parietal white matter. RESULTS: We found that Cho in the left frontal lobe was inversely correlated with Positive Affect [F(1,24) = 19.2, p <.001, r(2) =.45]. CONCLUSIONS: Our results highlight the important involvement of Cho underlying the integration of affective processing within prefrontal circuitry, and may indicate increased myelin turnover in subjects with lower Positive Affect. Further efforts will be necessary to determine if high Cho is associated with increased incidence of mood disorders throughout life.

Adult↗

Fluctuating asymmetry and the human brain.

Adaptive development requires the organism to resist genetic and environmental stresses that disrupt the genetic plan for growth, a buffering capacity termed developmental stability. Developmental instability is revealed by fluctuating asymmetry (FA), which has been demonstrated in many species to reflect phenotypic and genetic quality. We report (1) that a measure of developmental instability based on body FA predicts deviation from typical brain asymmetry, (2) that a combined measure of atypical brain asymmetry and body FA correlated negatively with the area of the corpus callosum, especially the portion connecting the left and right planum temporale, and (3) that this combined measure also predicted atypical asymmetry of the size of the somatosensory representation of the two hands, as determined from magnetic source imaging.

Journal Article↗