Research

ABSTRACT: Reduction of von Economo neurons in callosal agenesis. Jason A. Kaufman, Lynn K. Paul, and John M. Allman. (2006). Society for Neuroscience Annual Meeting.

Agenesis of the corpus callosum (AgCC) can have significant effects on social and emotional behaviors, including alexithymia (the inability to express one's emotional state), difficulty intuiting the emotional states of others, and deficits in self- and social-awareness that can impair such capacities as humor, comprehension of non-literal or affective language, and social judgment. One component of the neural network that supports social cognition which may be damaged in AgCC are the von Economo neurons, which are large spindle-shaped neurons localized to two brain regions that are known to be involved in social and emotional cognition: anterior cingulate cortex and fronto-insular cortex. von Economo neurons appear late in development (emerging mainly postnatally) and are a recent phylogenetic specialization, and as a consequence they may be particularly vulnerable to neuropoathologies. To test the hypothesis that von Economo neurons are selectively vulnerable in AgCC, we used stereology to obtain unbiased estimates of total neuron number and von Economo neuron number in postmortem brain specimens of two normal adult controls and two adults with isolated callosal dysgenesis: one case of complete callosal agenesis and one case of partial callosal agenesis in which only the genu and rostral 1/3 of the body of the corpus callosum were intact. In both anterior cingulate cortex and fronto-insular cortex, the partial agenesis case displayed approximately half as many von Economo neurons (~30,000 in fronto-insular cortex, ~50,000 in anterior cingulate cortex) as in the two normal controls (~75,000 in fronto-insular cortex, ~120,000 in anterior cingulate cortex). In the complete agenesis case the von Economo neurons were almost entirely absent (~3,200 in fronto-insular cortex, ~16,400 in anterior cingulate cortex). Most importantly, the ratio of total neurons to von Economo neurons changes dramatically in callosal agenesis. In the two control cases, the ratio of all neurons to von Economo neurons is approximately 100:1. In the partial AgCC case, the ratio increases to approximately 200:1, while in the complete AgCC case the ratio reaches approximately 1,000:1. These results indicate that von Economo neurons are selectively vulnerable in AgCC. Additionally, complete AgCC appears to be more detrimental to the von Economo neuron population than partial AgCC, suggesting that even a limited corpus callosum may provide a sustaining connection for the von Economo neuron population. We conclude that abnormal brain development can have a particularly harmful effect on von Economo neurons, and that their vulnerability could help to explain some social and emotional deficits that are seen in a variety of neuropathologies.

Sample functional magnetic resonance imaging project

Functional magnetic resonance imaging during finger tapping. fMRI during finger tapping. We can compare the activity in the areas of the brain that control motor activity (in this case finger tapping) between acallosal subjects and normal subjects with an intact corpus callosum. Many AgCC subjects have difficulty keeping both hands from moving when attempting to perform a task with one hand alone. This so-called "motor overflow" may be visible in fMRI as an increase in activity (a-c left column) relative to that seen in normal subjects (a-c right column). Strong activity in both motor areas is often seen in AgCC brains even for single handed tasks (a & b left column). Functional MRI detects small changes in the oxygenation of blood resulting from activity in the neurons of the brain. Maps of these changes are typically overlaid on high resolution MR images and can also be visualized in three dimensions (d).

Another study involves recording eye-tracking and psychophysiological measurements (galvanic skin response, heart rate, and respiration rate) while the participant looks at an emotionally intense social scene. Psychophysiological measures are a physical representation of the participant's emotional arousal. Preliminary studies suggest that while physiological arousal may be intact, individuals with AgCC give less emotionally intense ratings than controls.

Processing emotional facial expressions. AgCC subjects performed less accurately than controls in naming the emotion. Fixation density maps are shown for an AgCC subject (a) and a normal control (b), red indicates greatest number of fixations, plum the least.

Galvanic skin response and ratings to emotionally arousing scenes. 9 subjects with AgCC and 9 controls were presented with 15 emotionally charged pictures (pleasant, aversive, neutral). Ratings of emotional category (a) and ratings of the picture intensity (b) showed a compressed range and poor discrimination in the AgCC subjects (y-axis) compared to the controls (x-axis). Emotion category ratings correlated at 0.87, intensity ratings at 0.5, and significant differences between groups were verified using analysis of variance statistics. By contrast, robust galvanic skin responses were obtained in AgCC (c shows response to a pleasant slide). Also in AgCC subjects, the degree of physiological arousal, as measured by galvanic skin response, discriminated emotion categories (pleasant, aversive, neutral) using a resampling statistic (P<0.03 and P<0.07) of emotion categories compared to neutral; figure (d). (Click on the graphs to enlarge)