Shared temporoparietal dysfunction in dyslexia and typical readers with discrepantly high IQ

It is currently believed that reading disability (RD) should be defined by reading level without regard to broader aptitude (IQ). There is debate, however, about how to classify individuals who read in the typical range but less well than would be expected by their higher IQ. We used functional magnetic resonance imaging (fMRI) in 49 children to examine whether those with typical reading ability, but discrepantly low relative to IQ, show dyslexia-like activation patterns during reading. Children who were typical readers with high-IQ discrepancy showed reduced activation in left temporoparietal neocortex relative to two control groups of typical readers without IQ discrepancy. This pattern was consistent and spatially overlapping with results in children with RD compared to typically reading children. The results suggest a shared neurological atypicality in regions associated with phonological processing between children with dyslexia and children having typical reading ability that is substantially below their IQ

Female-specific intergenerational transmission patterns of the human corticolimbic circuitry

Parents have large genetic and environmental influences on offspring’s cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. We therefore examined human parent-offspring association in this neurocircuitry, and investigated the degree of association in gray matter volume between parent and offspring. We used voxel-wise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional grey matter volume in the corticolimbic circuit including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression, and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations, and provide promising ways to investigate intergenerational transmission patterns in the human brain

Dynamic Properties of Dopamine Asymmetry: A Basis for Functional Lateralization

Functional asymmetries, most commonly associated in humans with population-level hand preference and lateralization in language processing, are complex, heterogeneous traits with poorly understood biological and genetic bases. Notably, functional asymmetries are also associated with familial non-right handedness suggesting that common genetic factors influence both handedness and functional lateralization. This dissertation has two aims. The first is the development of a specific biological hypothesis that may partially account for the consistent co-lateralization of hand preference and prefrontal language function. I argue that asymmetries in local neural properties that affect the excitability and signal-to-noise ratio of neural assemblies can produce a bias in the direction and, to some extent, the degree of functional lateralization for complex functions. At a high level of representation, this hypothesis is similar to long-standing theories of hemispheric differences, but differs from these by providing a single biological difference between hemispheres that influences both motor and prefrontal asymmetries. Specifically, I propose that a hemispheric asymmetry in the ratio of activity at D1 and D2 dopamine receptors can account for both forms of asymmetry. The second aim is to identify novel electrophysiological and behavioral correlates of genetic effects linked to handedness. By applying a standard genetic model to familial handedness data, I obtain an estimate of these genetic effects for individual research participants that may improve sensitivity over previous studies that have primarily used categorical classifications to study familial handedness effects. Two EEG studies of executive function provide evidence for computational changes associated with familial handedness. The first, an auditory oddball paradigm, suggests that cortical noise is increased in conjunction with estimated genetic effects associated with left handedness. In the second study, a go-nogo task, a dissociation between response inhibition and response conflict processing was found with respect to estimated genetic effects associated with left handedness. In addition to bearing on current theories of conflict processing, these results may provide indirect evidence for dopaminergic contributions to neurological and behavioral differences associated with familial sinistrality. Additional studies of resting EEG and behavioral responses to Necker cube viewing provide additional evidence for broad effects of familial sinistrality