|
Professor, Department Chair Degree Received Research Interests Clinical and experimental neuropsychology. Specific ongoing lines of research include: 1. Individual differences in brain organization: investigation of the major dimensions of differences among human brains, including intelligence, sex, age, handedness and anatomical cerebral asymmetries. See publications 1, 4, 6, 9, 10, 14, 16, 20, 21, 23, 25, 26. A key construct in much of this work is “developmental stability”. This refers to an organism’s ability to develop the appropriate species-specific phenotype, despite genetic and environmental perturbations that tend to disrupt development, such as mutations, inbreeding, toxins, pathogens, parasites, injuries, starvation, and prenatal maternal stress. Developmental stability is analogous to a builder’s ability to turn a blueprint (the genotype) into a well-constructed house (the phenotype). A major discovery in biology and evolutionary psychology has been that individuals show differences in developmental stability: some individuals grow adaptive phenotypes under almost any conditions, whereas others show disrupted development given the slightest perturbations. These individual differences show moderate heritability. At the level of morphological development, one key manifestation of developmental stability is body symmetry. Confusingly, this is usually operationalized as the converse of developmental stability, called developmental instability, which is indexed by a measure called fluctuating asymmetry (FA). FA refers to deviation from perfect symmetry in bilateral traits that are symmetrical at the population level. FA negatively predicts (i.e. body symmetry positively predicts): health, fecundity, the quality of fitness-related traits, social dominance, and mating success across many species, including humans, though there is substantial variability in the strengths of associations across studies, and the reasons for this remain poorly understood. Another measure of developmental stability is through assessment of “minor physical anomalies” (or MPAs), various features of the face, head, hands, etc. that reflct slowed prenatal growth. An example of this research approach is shown in the figure below. On the X-axis is relative hand skill, with modal, moderate right-handedness as the low point in the center. On the Y-axis is a composite measure of FA and MPAs. Each dot represents a group of more tha 20 individuals. As one deviates from normal handedness, markers of developmental instability increase. We argue that this relationship suggests that (1) it is the tendency to deviate from normality that is heritable, rather than any directional tendency, (2) there is a polygenic basis to individual variation in handedness, and (3) helps explain why measures of atypical lateralization, including handedness, are so often seen in neurodevelopmental disorders.
2. Magnetic resonance spectroscopy (MRS) investigations of the neurochemical correlates of brain injury, intelligence, and mood. See publications 5, 7, 8. 11, 12, 13, 15, 17, 18. Magnetic Resonance Spectroscopy (MRS), investigates in vivo brain chemistry using conventional MR scanners; proton MRS (1H MRS) in particular has become widely used. In 1H
MRS the most commonly measured neurometabolites reflect peaks
arising from N-acetylaspartate and other N-acetyl groups (NAA),
myo-inositol (mI), creatine-phosphocreatine (Cre) and choline
(Cho) containing compounds. Other peaks arise from lactate, glutamine,
glutamate, GABA, macromolecules, and lipids. NAA is the strongest
peak in the adult proton MR spectrum and it is localized almost
entirely to neuronal bodies and axons. Reduced NAA levels have
been noted in many conditions, including normal aging and Alzheimer’s
disease, suggesting neuronal injury or death. The Cre peak represents
a measure of intracellular creatine and phosphocreatine, providing
a measure of cellular energy currency. The Cho peak reflects
all MRS visible choline moieties not bound to cell membranes,
and these are thought to be involved in membrane synthesis and
production of acetylcholine. Elevated Cho levels may indicate
inflammation or demyelination. 1H MRS studies vary
in at least two important ways. Some studies, especially more
recent ones, provide estimates of the absolute concentrations
of neurometabolites, while others represent concentrations as
ratios, most often with Cre as the denominator. Studies also vary in the size, locus,
and number of brain voxels assessed.
In diverse studies greater NAA concentrations have predicted better cognitive performance. For example, we have shown that NAA is strongly correlated with neurocognitive function in patient populations, such as traumatic brain injury and neuropsychiatric lupus erythematosus. Moreover, findings in normal control population also reveal substantial correlations between NAA and neurocognitive function (including IQ) and between Cho and mood. Below is a figure from ongoing research. The brain of a child with traumatic brain injury is displayed, with color-coded intensity maps for concentrations of the rations of Cho/Cre and NAA/Cre. This young man suffered a left hemisphere injury. Note the asymmetry of concentrations shown in panels B and C. The injured hemisphere is characterized by higher Cho/Cre and lower NAA/Cre.
3. Biological bases of neurodevelopmental disorders: schizophrenia, dyslexia, attention deficit/hyperactivity disorder. See publications 2, 3, 9, 16, 19, 22, 24. Below are a couple figures from our recent
studies of ADHD. We
observed smaller superior prefrontal volumes in ADHD children,
but no difference in inferior frontal volumes. We
also found that girls with ADHD, but not boys with ADHD had reduced
right prefrontal NAA.
List of Recent Publications
|
